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FUNDAMENTALS OF CANCER
BIOLOGY

S. KOUSIK SARAVANA

Abhayam Publishers
No.19, First street, AKG Nagar , Uppilipalayam,
Coimbatore ,Tamil Nadu , India

1
Fundamentals of cancer biology
Author : S.Kousik Saravana
E mail : [email protected]

Published by
Abhayam Publishers
No.19, first street, AKG Nagar , Uppilipalayam,Coimbatore
,Tamilnadu , India

ISBN 978-81-959205-0-1

MRP :Rs 350

2
 Acknowledgment
I thank the Almighty for creating the wisdom, space, and time.
I thank my family for the space and time. I acknowledge our Doctors and Professor Who
have sown the laws and thought of Medical science in my minds and heart
My special thanks to Dr.V.Dooslin Mercy Bai and Dr.R.V.Shalini for supporting me and
encouraging my work
And, I thank my Institution, Health care centre and university who helped me to cohere the
idea which is sown in this book

3
 Disclaimer
Care has been taken to confirm the accuracy of information presented in this book. The
Author and the Publisher, However, Cannot accept any responsibility for errors or omission
or for consequences from Application, Diagnoses and Treatment of the information in this
book and make no warranty, express or implied, with respect to this contents

4
 PREFACE

Cancer is a complex and multifaceted disease that affects millions of people

worldwide. It is one of the leading causes of death globally, accounting for
approximately 10 million deaths each year. The study of cancer biology is critical
to understanding the underlying mechanisms of the disease and developing
effective treatments.
The Fundamentals of Cancer Biology provides an essential introduction to the
biology of cancer. It covers the basic principles of cell biology and genetics, the
molecular mechanisms that contribute to cancer development and progression,
and the various factors that influence the growth and spread of cancer cells.
This book also explores the different types of cancer and their unique
characteristics, as well as the major risk factors associated with the disease. It
delves into the role of the immune system in cancer and the use of immunotherapy
in cancer treatment. In addition, the Fundamentals of Cancer Biology examines
the current approaches to cancer diagnosis, including imaging and molecular
techniques, and the various treatments available, such as surgery, radiation
therapy, and chemotherapy. It also covers emerging therapies, including targeted
therapy and gene therapy, and the challenges associated with drug resistance.
This book is designed for students and researchers in the fields of biology,
medicine, and oncology, as well as anyone interested in gaining a deeper
understanding of cancer biology. It provides a comprehensive overview of the
field and serves as a foundation for further study and research.
Finally, The Fundamentals of Cancer Biology is an invaluable resource for
anyone seeking to understand the complexities of cancer and the ongoing efforts
to combat this devastating disease.
Keep reading
The Author
S. Kousik Saravana [UG-Student , Department of B-Medical , Sri Shakthi Institutions-L&T By-pass,Sri
Shakthi Nagar Post, Sri Shakthi University, Chinniyampalayam, Coimbatore,Tamil Nadu 641062 ]

Email: [email protected]
Contact no : 9843331284

5
 MY SPECIAL THANKS TO

Prof. Dr VISWANATHAN SETHURAMAN

FRCS-General Surgery, MD -Obstetrics & Gynaecology, DGO, FRCS, FMA

PhD -Yoga,PG-Diploma in Psyco Neurobics & Memory Development

Medical Director ZI Clinic

Former Prof | HOD OF OBG &MEDICAL superintendent |Founder Director Centre for Yoga Studies,
Annamalai University

PRASIDDHA VISHNUSANKAR M.Sc IT

FOUNDER-CEO AIMS ACADEMY | DIRECTOR – ARCOMM POLLACHI

RAJEEV GNANAVEL

Bsc (Hons). Agriculture

FOUNDER – CEO COAT SUIT VIVASAYI

Faculty of Agriculture ,Annamalai University,

Annamalai nagar, chidambaram – 608002

6
 TABLE OF CONTENTS

ACKNOWLEDGMENT
PREFACE
1. OVERVIEW OF CANCER BIOLOGY

1.1 INTRODUCTION
1.2 ETIOLOGY OF CANCER
1.3 TYPES OF CANCER
1.4 ANATOMY OF CANCER CELLS
1.5 HISTOPATHOLOGY OF CANCER

2. CANCER METASTASIS

2.1 INTRODUCTION
2.2 HISTORY OF METASTASIS
2.3 SEQUENTIAL STEPS OF METASTASIS
2.4 STAGES OF METASATSIS

3. TUMOR FORMATION
3.1 UNCONTROLLED CELL DIVISION
3.2 NEOANGIOGENESIS (new blood vessels formation in cancer)
3.3 PRIMARY TUMOR GROWTH

4. AVOIDANCE OF CELL DEATH

4.1 APOPTOSIS
4.2 OCCURANCE OF APOPTOSIS
4.3 DIAGNOSIS AND STAGES

5. TREATMENT
5.1 PRECISION MEDICINE
5.2 SURGERY
5.3 CHEMOTHERAPHY
5.4 IMMUNOTHERAPY

BIBLOGRAPHY
GLOSSARY

7
8
 CHAPTER 1
OVERVIEW OF CANCER BIOLOGY

1.1 INTRODUCTION
Cancer is a complex and multifaceted disease that affects millions of people
worldwide. It is characterized by the uncontrolled growth and spread of
abnormal cells in the body, which can lead to the formation of tumors and
the invasion of surrounding tissues. Cancer can occur in any part of the body
and can affect people of all ages, although the risk increases with age.The
study of cancer biology is critical to understanding the underlying
mechanisms of the disease and developing effective treatments. Cancer
biology encompasses a wide range of topics, including the basic principles
of cell biology and genetics, the molecular mechanisms that contribute to
cancer development and progression, and the various factors that influence
the growth and spread of cancer cells.
One of the key features of cancer cells is their ability to evade the normal
controls that regulate cell growth and division. Normal cells divide in a
controlled manner, with the timing and frequency of cell division tightly
regulated by a complex network of signaling pathways. In contrast, cancer
cells have acquired mutations in the genes that regulate these pathways,
allowing them to bypass these controls and divide uncontrollably.

FIGURE:01
One of the most common mutations found in cancer cells is in the tumor
suppressor genes, which normally act as a brake on cell division. When

9
these genes are mutated, the brakes are released, allowing cells to divide and
proliferate unchecked. Mutations in other genes that control cell growth,
such as oncogenes, can also contribute to the development of cancer.In
addition to these genetic mutations, cancer cells also have altered
metabolism and signaling pathways that enable them to survive and
proliferate in hostile environments. Cancer cells often have a high demand
for energy and nutrients, and they can alter their metabolism to meet these
demands. For example, many cancer cells have a preference for glycolysis,
a process that generates energy in the absence of oxygen, even when oxygen
is available.
Cancer cells can also alter their signaling pathways to promote cell survival
and proliferation. For example, they may activate the PI3K/Akt/mTOR
pathway, which is involved in cell growth and metabolism, or the
Ras/MAPK pathway, which is involved in cell proliferation and survival.
These pathways can be targeted by drugs to slow or stop cancer growth.
The development and progression of cancer is also influenced by a wide
range of external factors, including environmental exposures, lifestyle
factors, and underlying medical conditions. Exposure to carcinogens, such
as tobacco smoke, radiation, and certain chemicals, can increase the risk of
cancer. Lifestyle factors, such as diet, exercise, and alcohol consumption,
can also affect cancer risk.
One of the most important external factors influencing cancer development
is the immune system. The immune system plays a critical role in
recognizing and eliminating cancer cells, and defects in the immune system
can increase the risk of cancer. In addition, some cancers can suppress the
immune system or evade immune detection, allowing them to grow and
spread.
The study of cancer biology is important not only for understanding the
underlying mechanisms of the disease but also for developing effective
treatments. Cancer treatments typically aim to target the unique features of
cancer cells while sparing normal cells, and they can include surgery,
radiation therapy, chemotherapy, and targeted therapy.
Surgery is often the first line of treatment for solid tumors, and it involves
removing the cancerous tissue. Radiation therapy uses high-energy radiation
to kill cancer cells or prevent their growth, and it can be delivered externally

10
or internally. Chemotherapy involves using drugs to kill cancer cells, and it
can be administered orally or intravenously. Targeted therapy uses drugs that
target specific molecular pathways involved in cancer growth and
proliferation.
In recent years, there has been a growing interest in immunotherapy, which
involves using the immune system to fight cancer. Immunotherapy can take
several forms, including checkpoint inhibitors, which target proteins on
immune cells that inhibit their activity, and adoptive cell therapy

1.2 ETIOLOGY OF CANCER

Etiology is the study of the causes or origins of a disease or medical
condition. It involves the investigation of the various factors that contribute
to the development and progression of the disease. The term is commonly
used in medical and scientific fields to describe the underlying causes of a
particular condition, and is often used interchangeably with the term
"pathogenesis". Understanding the etiology of a disease is important for the
development of effective treatment and prevention strategies. Factors that
may be considered in the etiology of a disease include genetic,
environmental, and lifestyle factors.
The etiology of cancer refers to the various factors that contribute to the
development and progression of the disease. Cancer is a complex and
multifaceted disease, and its etiology involves a wide range of genetic,
environmental, and lifestyle factors.
Genetic factors
Genetic mutations are one of the most important factors in the etiology of
cancer. Mutations in specific genes can disrupt the normal cellular processes
that regulate cell growth and division, leading to the uncontrolled
proliferation of cells. These mutations can be inherited or acquired through
exposure to various environmental factors.
Inherited mutations in specific genes, such as BRCA1 and BRCA2, are
associated with an increased risk of developing breast and ovarian cancer.
Similarly, mutations in the TP53 gene, which is involved in DNA repair and

11
cell cycle regulation, can increase the risk of developing several types of
cancer, including breast, colon, and lung cancer.
Acquired mutations can also contribute to cancer development. Exposure to
environmental factors, such as tobacco smoke, radiation, and certain
chemicals, can damage DNA and lead to mutations. In addition, errors
during DNA replication or repair can also result in mutations.
Environmental factors
Environmental factors can play a significant role in the development of
cancer. Exposure to certain substances, such as tobacco smoke, alcohol, and
certain chemicals, can increase the risk of cancer development. For
example, smoking is a major risk factor for lung cancer, while alcohol
consumption is a risk factor for liver cancer.
Exposure to ionizing radiation, such as X-rays and gamma rays, can also
increase the risk of cancer. This type of radiation can damage DNA and lead
to mutations, which can contribute to cancer development. People who work
in occupations that involve exposure to radiation, such as nuclear workers
and radiologists, are at increased risk of developing cancer.
Other environmental factors that may increase the risk of cancer include air
pollution, water pollution, and exposure to certain viruses and bacteria. For
example, the human papillomavirus (HPV) is associated with an increased
risk of cervical cancer, while the hepatitis B and C viruses are associated
with an increased risk of liver cancer.
Lifestyle factors
Lifestyle factors, such as diet, physical activity, and body weight, can also
influence the development of cancer. A diet high in red and processed meats,
for example, has been linked to an increased risk of colorectal cancer. In
contrast, a diet high in fruits, vegetables, and whole grains may reduce the
risk of several types of cancer.Physical activity is also important for
reducing the risk of cancer. Regular exercise can help maintain a healthy
body weight and reduce inflammation, both of which are associated with a
lower risk of cancer. In addition, physical activity may help reduce the risk
of several types of cancer, including breast, colon, and prostate cancer.

12
Body weight is also an important factor in the etiology of cancer. Obesity is
associated with an increased risk of several types of cancer, including breast,
colon, and kidney cancer. This may be due in part to the fact that obesity
can lead to chronic inflammation and insulin resistance, both of which are
associated with an increased risk of cancer.
Other lifestyle factors that may increase the risk of cancer include alcohol
consumption, tobacco use, and exposure to sunlight. Excessive alcohol
consumption is associated with an increased risk of several types of cancer,
including breast, liver, and esophageal cancer. Tobacco use is a major risk
factor for several types of cancer, including lung, bladder, and pancreatic
cancer. Exposure to sunlight can also increase the risk of skin cancer,
particularly if sunburns are frequent or severe.In conclusion, the etiology of
cancer is complex and multifaceted, involving a wide range of genetic,
environmental, and lifestyle factors. Understanding these factors is critical
for developing effective strategies for cancer prevention and treatment

FIGURE : 02

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1.3 TYPES OF CANCER

Cancer is a group of diseases characterized by uncontrolled growth and

spread of abnormal cells in the body. There are many types of cancer, each
of which can affect different organs and tissues in the body. Some of the
most common types of cancer include:
Breast cancer:
Breast cancer is the most common cancer among women worldwide. It
develops in the breast tissue and can be detected through mammograms,
self-exams, and other screening methods. Risk factors for breast cancer
include genetics, age, and lifestyle factors such as alcohol consumption and
obesity.
Lung cancer:
Lung cancer is the leading cause of cancer-related deaths in both men and
women worldwide. It is often caused by long-term exposure to tobacco
smoke, and other risk factors include exposure to radon and air pollution.
Symptoms of lung cancer can include coughing, chest pain, and shortness
of breath.
Prostate cancer:
Prostate cancer is the most common cancer among men in the United States.
It develops in the prostate gland, which is a small gland in the male
reproductive system. Risk factors for prostate cancer include age, family
history, and certain genetic mutations. Symptoms of prostate cancer may
include difficulty urinating, blood in the urine, and erectile dysfunction.
Colorectal cancer:
Colorectal cancer develops in the colon or rectum, which are parts of the
digestive system. It is the third most common cancer in both men and
women in the United States. Risk factors for colorectal cancer include age,
family history, and lifestyle factors such as a diet high in red meat and low
in fiber. Symptoms of colorectal cancer may include changes in bowel
habits, abdominal pain, and rectal bleeding.

14
Skin cancer:
Skin cancer is the most common type of cancer in the United States. It
develops in the cells that make up the skin and can be caused by exposure
to ultraviolet (UV) radiation from the sun or tanning beds. Risk factors for
skin cancer include fair skin, a history of sunburns, and a family history of
the disease. Symptoms of skin cancer may include changes in the
appearance of moles or other skin lesions.
Bladder cancer:
Bladder cancer develops in the bladder, which is a hollow organ in the lower
abdomen that stores urine. Risk factors for bladder cancer include age,
smoking, exposure to certain chemicals, and a history of bladder infections.
Symptoms of bladder cancer may include blood in the urine, pain during
urination, and frequent urination.
Leukemia:
Leukemia is a type of cancer that develops in the blood and bone marrow,
which are the tissues that produce blood cells. There are several types of
leukemia, each of which affects different types of blood cells. Risk factors
for leukemia include exposure to radiation and certain chemicals, as well as
certain genetic mutations. Symptoms of leukemia may include fatigue,
fever, and easy bruising or bleeding.
Lymphoma:
Lymphoma is a type of cancer that develops in the lymphatic system, which
is part of the immune system. There are several types of lymphoma, each of
which affects different types of immune cells. Risk factors for lymphoma
include exposure to certain chemicals and infections with certain viruses.
Symptoms of lymphoma may include swollen lymph nodes, fatigue, and
unexplained weight loss.
Pancreatic cancer:
Pancreatic cancer develops in the pancreas, which is a gland in the abdomen
that produces digestive enzymes and hormones. It is one of the deadliest
types of cancer, with a low survival rate. Risk factors for pancreatic cancer
include age, smoking, and certain genetic mutations. Symptoms of
pancreatic cancer may include abdominal pain, jaundice, and weight loss.

15
there are many types of cancer that can affect different organs and tissues in
the body

1.4 ANATOMY OF CANCER CELLS

Cancer is a complex disease that can affect any part of the body. It starts
when cells in a specific tissue or organ grow abnormally and divide out of
control, forming a mass or tumor. The tumor can be benign (non-cancerous)
or malignant (cancerous).
The structure of cancer can vary depending on the type and stage of the
disease. In general, cancer cells have abnormal features that distinguish
them from normal cells. These features can include changes in cell size and
shape, loss of specialized cell functions, and alterations in the way cells
communicate with each other.
As cancer cells continue to divide and grow, they can invade nearby tissues
and organs, and spread to other parts of the body through the bloodstream
or lymphatic system. This process is called metastasis and can lead to the
formation of secondary tumors in other parts of the body.
The structure of a cancerous tumor also includes a microenvironment
composed of blood vessels, immune cells, and other types of cells that
support tumor growth and survival. This microenvironment can play a
crucial role in the progression and response of the tumor to treatment.
Overall, the structure of cancer is complex and dynamic, with changes
occurring at the cellular and molecular levels as the disease progresses.
Understanding the structure and behavior of cancer cells is crucial for
developing effective treatments and improving outcomes for patients with
cancer

16
 FIGURE:03

1.5 HISTOPATHOLOGY OF CANCER

Histopathology is the study of the microscopic features of diseased tissues.
It is an essential tool in the diagnosis and management of cancer.
Histopathology allows pathologists to examine the structure of cancer cells
and tissues and determine the extent and severity of the disease.
In the case of cancer, histopathology involves the examination of tissue
samples taken from the tumor and surrounding areas. These samples are
typically obtained through a biopsy or surgical resection. The pathologist
examines these samples under a microscope and looks for changes in the

17
cells and tissues that are indicative of cancer. The pathologist may also
perform additional tests to identify specific molecular markers that can help
with diagnosis and treatment planning.
One of the key features of cancer that can be seen on histopathology is the
presence of abnormal cells. Cancer cells often have an abnormal shape and
size, and may have features such as enlarged nuclei, increased mitotic
activity (indicating rapid cell division), and loss of cell differentiation
(meaning the cells no longer resemble normal cells of the tissue they came
from). These changes can be used to classify the tumor as a specific type of
cancer and determine its grade, which is a measure of how abnormal the
cells appear.
There are many different types of cancer, each with its own distinct
histopathological features. Some of the most common types of cancer
include:
Carcinoma: This type of cancer arises from cells in the epithelial tissue,
which is the lining of the body's internal and external surfaces. Carcinomas
can occur in many different organs, including the lungs, breast, prostate, and
colon. Histopathological features of carcinomas may include the presence
of glandular structures, the formation of solid nests or sheets of cells, and
the appearance of keratinized cells (in some cases).
Sarcoma: This type of cancer arises from cells in the mesenchymal tissue,
which includes bone, muscle, and connective tissue. Sarcomas can occur in
many different parts of the body, including the bones, soft tissues, and
organs such as the uterus. Histopathological features of sarcomas may
include the presence of spindle-shaped cells, the formation of cartilage or
bone-like structures, and the appearance of large, pleomorphic cells (in
some cases).
Leukemia and lymphoma: These types of cancer arise from cells in the
blood or lymphatic system. Leukemias are cancers of the white blood cells,
while lymphomas are cancers of the lymphatic system. Histopathological
features of these types of cancer may include the presence of abnormal cells
in the blood or lymph nodes, respectively.
Histopathology can also be used to determine the extent of cancer spread,
or metastasis. Pathologists look for evidence of cancer cells in nearby tissues

18
and lymph nodes, which can indicate the likelihood of the cancer spreading
to other parts of the body. In addition, histopathology can be used to
examine tissue samples from other parts of the body to look for evidence of
secondary tumors, which can indicate that the cancer has spread.
In some cases, histopathology can also provide information about the
prognosis (expected outcome) of the cancer. For example, certain molecular
markers may be associated with a better or worse prognosis, which can help
guide treatment decisions. In addition, the stage of the cancer (which is
based on the size and extent of the tumor, as well as the presence or absence
of metastasis) can also provide important prognostic information.
Histopathology is an essential tool in the diagnosis and management of
cancer. It allows pathologists to examine the structure of cancer cells and
tissues in detail, providing information about the type, grade, and extent of
the disease. This information can help guide treatment decisions and provide
important prognostic information for patients. In addition, ongoing

19
 CHAPTER 2
CANCER METASTASIS

2.1 INTRODUCTION
Cancer metastasis is the process by which cancer cells spread from
the site of origin to other parts of the body. It is a complex and multifactorial
process that involves many different steps, including the invasion of
surrounding tissues, the entry into the bloodstream or lymphatic system, and
the colonization of distant organs.
Metastasis is a major cause of cancer-related deaths, as it often occurs after
the cancer has already spread and become difficult to treat. Understanding
the mechanisms underlying cancer metastasis is therefore essential for the
development of new and effective cancer therapies.
Mechanisms of Cancer Metastasis
The metastatic process is a multi-step process that involves the interaction
of cancer cells with the surrounding tissue microenvironment. The first step
in this process is the invasion of surrounding tissues by cancer cells. This
involves the degradation of the extracellular matrix (ECM) by enzymes such
as matrix metalloproteinases (MMPs) and cathepsins, which allows cancer
cells to penetrate into nearby tissues.
Once cancer cells have invaded surrounding tissues, they may enter the
bloodstream or lymphatic system. This process is facilitated by the secretion
of chemokines and growth factors by cancer cells, which attract blood
vessels and lymphatic vessels to the site of the tumor. Cancer cells may also
hijack the normal processes of angiogenesis (the formation of new blood
vessels) and lymphangiogenesis (the formation of new lymphatic vessels)
to promote their own growth and spread.
Once cancer cells enter the bloodstream or lymphatic system, they are
carried to distant organs. The process of metastasis is not random, and
certain organs are more likely to be targeted by specific types of cancer. For

20
example, breast cancer often metastasizes to the lungs, liver, and bones,
while prostate cancer often metastasizes to the bones.
Upon arrival at a distant organ, cancer cells may encounter a hostile
microenvironment. This microenvironment may include a lack of
appropriate nutrients, oxygen, or growth factors, as well as an immune
response from the host organism. Cancer cells that are able to survive and
adapt to this new microenvironment may then begin to proliferate and form
secondary tumors.
Factors Influencing Cancer Metastasis
The metastatic process is influenced by many different factors, both intrinsic
(related to the cancer cells themselves) and extrinsic (related to the
surrounding tissue microenvironment).
Intrinsic factors that can influence cancer metastasis include the genetic and
epigenetic alterations that occur in cancer cells. These alterations may affect
the expression of genes involved in the regulation of cell adhesion,
migration, and invasion. For example, mutations in the tumor suppressor
gene TP53 are commonly found in many different types of cancer, and are
associated with increased metastatic potential.
Extrinsic factors that can influence cancer metastasis include the
composition and structure of the surrounding tissue microenvironment. For
example, the presence of certain cell types, such as cancer-associated
fibroblasts, immune cells, and endothelial cells, can promote or inhibit
cancer metastasis. In addition, factors such as hypoxia (low oxygen levels)
and inflammation can also promote cancer metastasis by altering the
expression of genes involved in cell adhesion, migration, and invasion.
Clinical Implications of Cancer Metastasis
The ability of cancer cells to metastasize is a major challenge in the
treatment of cancer. Metastasis often occurs after the cancer has already
spread, making it difficult to treat with conventional therapies such as
surgery, chemotherapy, and radiation therapy.
There are currently several strategies for preventing or treating cancer
metastasis. One approach is to target the molecular pathways involved in
the metastatic process. For example, drugs that target angiogenesis, such as

21
bevacizumab, have been developed to prevent the formation of new blood
vessels and inhibit the growth of tumors.

2.2 HISTORY OF METASTASIS

The concept of cancer metastasis has been recognized for centuries,
although our understanding of the underlying mechanisms has evolved
considerably over time. This article will provide a brief overview of the
history of metastasis, from its early recognition to current research on its
mechanisms and treatment.
Ancient Times
The earliest written record of cancer dates back to ancient Egypt, where a
description of breast cancer was found in the Edwin Smith papyrus, dated
around 1600 BC. However, there is little evidence of an understanding of
cancer metastasis in ancient times. In fact, many ancient medical theories
held that cancer was caused by an excess of black bile or other bodily fluids,
and that cancerous tumors were self-contained growths that did not spread
to other parts of the body.
Hippocrates and Galen
The ancient Greek physician Hippocrates (460-370 BC) is often credited
with the first recognition of cancer metastasis. He observed that tumors
could recur in different parts of the body after surgical removal, and
hypothesized that this was due to the spread of cancerous cells throughout
the body. His observations were later expanded upon by the Roman
physician Galen (130-200 AD), who described the spread of breast cancer
to the liver and other organs.
Renaissance and Enlightenment
During the Renaissance and Enlightenment periods, there was a renewed
interest in the study of anatomy and physiology, and the first anatomical
descriptions of metastatic cancer were published. In 1665, the English
physician Thomas Bartholin described the spread of cancer from the breast
to the axillary lymph nodes, and in 1679, the Italian physician Giovanni
Maria Lancisi described the spread of cancer from the colon to the liver.
18th and 19th Centuries

22
In the 18th and 19th centuries, there was a growing understanding of the
cellular basis of cancer, and the first histological descriptions of metastatic
tumors were made. In 1811, the French physician René Laennec described
the microscopic features of lung cancer, including the presence of tumor
cells in the lymphatic vessels. In 1829, the German pathologist Johannes
Müller described the microscopic features of metastatic tumors in the liver,
and in 1867, the English surgeon Stephen Paget proposed the "seed and soil"
hypothesis of metastasis, which suggested that certain cancers had a
predilection for specific organs.
20th Century
The 20th century saw a rapid expansion of knowledge about the
mechanisms of cancer metastasis, including the role of the immune system,
the cellular and molecular mechanisms of invasion and migration, and the
molecular pathways that regulate metastatic behavior.
In the early 1900s, the German pathologist Paul Ehrlich proposed the theory
of "tumor immunology," which suggested that the immune system played a
role in recognizing and eliminating cancer cells. This theory was later
expanded upon by the American immunologist Lloyd Old, who proposed
the concept of "cancer immunosurveillance," which suggested that the
immune system was constantly monitoring the body for cancer cells and
eliminating them before they could form tumors.
In the mid-1900s, there was a growing interest in the cellular and molecular
mechanisms of cancer metastasis. In 1953, the American pathologist James
Ewing described the "Ewing effect," which suggested that the growth of
metastatic tumors was dependent on the interaction between cancer cells
and the surrounding tissue microenvironment. In 1969, the American cell
biologist Elizabeth Hay described the process of "cellular locomotion,"
which explained how cancer cells could migrate through tissues and invade
other organs.

23
The Modern Era
In the 19th and early 20th centuries, advances in microscopy and histology
allowed researchers to study the structure and behavior of cancer cells in
more detail. Rudolf Virchow, a German physician and pathologist, was
among the first to use the microscope to study cancer cells. He observed that
cancer cells often had an irregular shape and size, and that they tended to be
more invasive than normal cells.
In the early 20th century, researchers began to develop animal models of
cancer metastasis. In 1906, the American physician James Ewing developed
a mouse model of cancer metastasis by injecting cancer cells into the tail
vein of mice. This model allowed researchers to study the spread of cancer
cells throughout the body in a controlled setting.
In the mid-20th century, advances in genetics and molecular biology
revolutionized our understanding of cancer metastasis. In the 1950s, the
British physician and scientist Peter Nowell proposed the concept of clonal
evolution, which suggested that cancer cells evolved over time through a
process of mutation and selection. This concept provided a framework for
understanding the genetic changes that occur during cancer metastasis.
In the 1960s and 1970s, researchers began to study the molecular
mechanisms underlying cancer metastasis in more detail. They identified a
number of genes and signaling pathways that were involved in the invasion
and spread of cancer cells, including matrix metalloproteinases (MMPs),
vascular endothelial growth factor (VEGF), and epidermal growth factor
receptor (EGFR).
In the 1980s and 1990s, advances in imaging technologies allowed
researchers to visualize cancer cells and tumors in living organisms.
Techniques such as computed tomography (CT), magnetic resonance
imaging (MRI), and positron emission tomography (PET) became widely
used in clinical practice, allowing doctors to detect and monitor cancer
metastasis in patients.
Recent Advances
In the 21st century, researchers have continued to make significant advances
in our understanding of cancer metastasis. The development of new imaging
techniques, such as multiphoton microscopy

24
2.3 SEQUENTIAL STEPS OF METASTASIS
Metastasis is a complex and multistep process that involves the
dissemination of cancer cells from the primary tumor to distant organs. The
process of metastasis can be broken down into several sequential steps, each
of which is essential for the successful spread of cancer cells throughout the
body.
Step 1: Invasion
The first step in metastasis is the invasion of cancer cells into surrounding
tissues. Cancer cells are able to invade surrounding tissues by breaking
down the extracellular matrix (ECM), which is a complex network of
proteins that provides structural support to tissues. Cancer cells secrete
enzymes such as matrix metalloproteinases (MMPs) that can degrade the
ECM, allowing them to penetrate into adjacent tissues.
Step 2: Intravasation
After invading surrounding tissues, cancer cells can enter into blood or
lymphatic vessels in a process called intravasation. This is facilitated by the
ability of cancer cells to break down the basement membrane, a specialized
ECM that lines blood and lymphatic vessels. Once inside the vessels, cancer
cells can be carried to distant organs.
Step 3: Circulation
Once in the bloodstream or lymphatic vessels, cancer cells can travel to
distant organs. However, the majority of circulating cancer cells are
eliminated by the immune system or become trapped in capillaries, and only
a small fraction of cells are able to survive and colonize distant organs.
Step 4: Extravasation
To establish a secondary tumor, cancer cells must be able to exit the
bloodstream or lymphatic vessels and invade into the surrounding tissue.
This process is known as extravasation and is facilitated by the ability of
cancer cells to adhere to the endothelial cells that line blood vessels. Cancer
cells can also use MMPs to break down the basement membrane and enter
the surrounding tissue.

25
Step 5: Colonization
Once cancer cells have extravasated into a distant organ, they must be able
to survive and establish a secondary tumor. This process, called
colonization, is facilitated by interactions between cancer cells and the
surrounding tissue. Cancer cells can secrete growth factors that stimulate
the growth of blood vessels, which in turn supply the tumor with nutrients
and oxygen.
Step 6: Growth and Progression
After colonization, the secondary tumor can continue to grow and progress.
This can be facilitated by the ability of cancer cells to evade the immune
system and to acquire additional genetic mutations that confer a growth
advantage. The growth and progression of the secondary tumor can lead to
further invasion, intravasation, circulation, and colonization, perpetuating
the cycle of metastasis.
The process of metastasis is a complex and multistep process that involves
the dissemination of cancer cells from the primary tumor to distant organs.
Each step of metastasis is essential for the successful spread of cancer cells,
and understanding the underlying mechanisms of metastasis is essential for
developing new treatments and improving patient outcomes.

26
2.4 STAGES OF METASTASIS
Metastasis is a complex process that involves the spread of cancer cells from
the primary tumor to other parts of the body. This process is divided into
several stages or steps, which are essential for the successful establishment
of secondary tumors.
Local Invasion stage, cancer cells break away from the primary tumor and
invade nearby tissues, such as lymph nodes or blood vessels. This process
is facilitated by the ability of cancer cells to secrete enzymes that break
down the extracellular matrix, which is a network of proteins that provides
structural support to tissues. Once cancer cells invade nearby tissues, they
can enter the bloodstream or lymphatic system.Once cancer cells have
invaded nearby tissues, they can enter the bloodstream or lymphatic system,
which allows them to travel to other parts of the body. This process is known
as intravasation and is facilitated by the ability of cancer cells to break down
the basement membrane, which is a specialized layer that separates the
bloodstream or lymphatic system from surrounding tissues.Once cancer
cells have entered the bloodstream or lymphatic system, they can travel to
distant organs. However, the majority of circulating cancer cells are
eliminated by the immune system, while others become trapped in
capillaries. Only a small fraction of circulating cancer cells are able to
survive and colonize distant organs.
To establish a secondary tumor, cancer cells must exit the bloodstream or
lymphatic system and invade surrounding tissues. This process is known as
extravasation and is facilitated by the ability of cancer cells to adhere to the
endothelial cells that line blood vessels. Cancer cells can also use enzymes
to break down the basement membrane and enter the surrounding
tissue.Once cancer cells have extravasated into a distant organ, they must be
able to survive and establish a secondary tumor. This process is known as
colonization and is facilitated by interactions between cancer cells and the
surrounding tissue. Cancer cells can secrete growth factors that stimulate
the growth of blood vessels, which in turn supply the tumor with nutrients
and oxygen., understanding the stages of metastasis is important for
developing strategies to prevent or treat metastatic cancer. Researchers are
working to identify key molecular mechanisms involved in each stage of
metastasis, with the aim of developing new drugs that can target these
mechanisms and prevent the spread of cancer cells. Early detection and

27
treatment of primary tumors can also help to prevent the development of
metastasis.

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 CHAPTER 3
TUMOR FORMATION

3.1 UNCONTROLLED CELL DIVISION

Cancer is a complex disease characterized by uncontrolled cell division and
the ability of cancer cells to invade and metastasize to distant organs.
Normal cells in the body undergo a tightly regulated process of cell division,
known as the cell cycle, which ensures that new cells are produced only
when needed and that damaged or abnormal cells are eliminated. Cancer
cells, on the other hand, have acquired mutations or alterations in key genes
that control the cell cycle, leading to uncontrolled cell division and the
formation of tumors.
The cell cycle is divided into several phases, including G1 (gap 1), S (DNA
synthesis), G2 (gap 2), and M (mitosis). In G1 phase, cells undergo growth
and metabolic activities to prepare for DNA replication in the S phase. In
G2 phase, the cell undergoes further growth and prepares for cell division
in the M phase. During mitosis, the cell divides into two daughter cells, each
with a complete set of chromosomes.
Normal cells have several mechanisms to ensure that the cell cycle proceeds
smoothly and that DNA damage or errors are repaired before cell division
occurs. One of these mechanisms is the control of cyclin-dependent kinases
(CDKs), which are enzymes that regulate the progression of the cell cycle
by phosphorylating target proteins. CDK activity is tightly controlled by the
levels of cyclins, which are proteins that bind to and activate CDKs at
specific stages of the cell cycle.
In cancer cells, alterations in genes that regulate the cell cycle can lead to
uncontrolled cell division and the formation of tumors. For example,
mutations in the tumor suppressor gene TP53, which encodes the p53
protein, are commonly found in many types of cancer. The p53 protein plays
a critical role in the cell cycle by activating DNA repair pathways or
inducing cell death (apoptosis) in response to DNA damage. When p53 is

29
mutated or absent, cells with DNA damage can continue to divide, leading
to the accumulation of mutations and the development of cancer.
Other genes that regulate the cell cycle, such as CDKs and cyclins, can also
be altered in cancer cells. For example, the CDK inhibitor p16INK4a is
frequently deleted or silenced in many types of cancer, leading to the
uncontrolled activation of CDKs and the cell cycle. In addition, some cancer
cells can produce their own growth factors, which stimulate cell division
and promote tumor growth.
Uncontrolled cell division in cancer cells can also lead to the loss of normal
cell functions and the acquisition of new characteristics, such as the ability
to invade surrounding tissues and metastasize to distant organs. Cancer cells
can undergo a process of epithelial-mesenchymal transition (EMT), which
involves changes in gene expression that enable cells to detach from the
primary tumor, invade surrounding tissues, and enter the bloodstream or
lymphatic system.
During EMT, cancer cells undergo changes in cell shape and adhesion, and
acquire the ability to degrade extracellular matrix proteins that normally
provide structural support to tissues. In addition, EMT is associated with the
acquisition of stem-like properties, such as self-renewal and resistance to
chemotherapy and radiation therapy., uncontrolled cell division is a
hallmark of cancer and is driven by alterations in genes that regulate the cell
cycle and cell division. Understanding the molecular mechanisms that
underlie these alterations is critical for developing new strategies to prevent
or treat cancer. Researchers are actively studying the role of specific genes
and proteins in the cell cycle and cell division, with the aim of developing
targeted therapies that can selectively inhibit cancer cell growth and prevent
the spread of cancer to other parts of the body.

30
 FIGURE:04

3.2 NEOANGIOGENESIS
Neoangiogenesis, also known as angiogenesis, is the process of formation
of new blood vessels from pre-existing ones. This process is critical for
normal development, wound healing, and tissue regeneration. However,
neoangiogenesis is also a critical process in the growth and spread of cancer.
In fact, angiogenesis is a hallmark of cancer, and tumor growth and
progression depend on the ability of cancer cells to induce the formation of
new blood vessels.
Angiogenesis is a complex process that involves a sequence of events that
are tightly regulated by a balance between pro-angiogenic and anti-
angiogenic factors. The process of angiogenesis begins with the activation
of endothelial cells, which are the cells that line the interior surface of blood
vessels. In response to pro-angiogenic signals, endothelial cells undergo
changes in their shape and behavior, leading to the formation of new blood
vessels.
In cancer, neoangiogenesis is a critical process that enables tumors to obtain
oxygen and nutrients necessary for their growth and survival. Tumor cells
secrete pro-angiogenic factors, such as vascular endothelial growth factor
(VEGF) and basic fibroblast growth factor (bFGF), which stimulate the
activation and proliferation of endothelial cells. Tumor cells also secrete
matrix metalloproteinases (MMPs), which degrade the extracellular matrix
(ECM) surrounding blood vessels, facilitating the migration of endothelial
cells and the formation of new blood vessels.

31
Once activated, endothelial cells undergo a series of steps to form new blood
vessels. These steps include the degradation of the basement membrane,
migration of endothelial cells towards the tumor, proliferation of endothelial
cells to form tubular structures, and recruitment of pericytes and smooth
muscle cells to stabilize the new blood vessels.
The new blood vessels formed by neoangiogenesis in tumors are abnormal
and dysfunctional. These blood vessels are highly permeable, allowing for
the leakage of plasma proteins and red blood cells into the surrounding
tissues, leading to the formation of edema and inflammation. The abnormal
blood vessels in tumors are also tortuous and disorganized, leading to poor
blood flow and hypoxia (low oxygen levels) in some areas of the tumor.
The role of neoangiogenesis in cancer is not limited to the growth and
survival of tumors. Neoangiogenesis is also critical for the spread of cancer
cells to distant organs, a process known as metastasis. Cancer cells that
detach from the primary tumor and enter the bloodstream or lymphatic
system require a blood supply to survive and proliferate in distant organs.
These cancer cells can induce the formation of new blood vessels in the
surrounding tissues, enabling them to establish secondary tumors in distant
organs.
The formation of new blood vessels in tumors is a complex process that
involves a balance between pro-angiogenic and anti-angiogenic factors. In
addition to pro-angiogenic factors, there are also several anti-angiogenic
factors that can inhibit neoangiogenesis in tumors. One of the best-known
anti-angiogenic factors is endostatin, which is a fragment of collagen XVIII
that inhibits the proliferation and migration of endothelial cells.
Several strategies have been developed to target neoangiogenesis in cancer
as a way to inhibit tumor growth and metastasis. One approach is to directly
target the pro-angiogenic factors secreted by tumor cells, such as VEGF and
bFGF. Drugs that target VEGF, such as bevacizumab, have been approved
for the treatment of several types of cancer, including colorectal, lung, and
kidney cancer.
Another approach to target neoangiogenesis in cancer is to target the
endothelial cells themselves. Several drugs have been developed that target
the receptors on endothelial cells that are involved in angiogenesis, such as
the VEGF receptor and the platelet-derived growth

32
 FIGURE:05
3.3 PRIMARY TUMOR GROWTH
Primary tumor growth refers to the uncontrolled proliferation of cancerous
cells at the site of origin. This process is the result of numerous genetic and
epigenetic alterations that have occurred in the cells, leading to their
uncontrolled growth and division. In the early stages of tumor growth, the
tumor cells remain confined to the original site, and the tumor is said to be
localized. However, as the tumor continues to grow, it can invade and
destroy nearby tissues and organs.
The growth of the primary tumor is influenced by numerous factors,
including the type of cancer, the stage of the disease, and the patient's overall
health. In general, cancer cells grow and divide more rapidly than normal
cells, which means that the primary tumor can grow quite quickly. However,
the rate of growth varies from tumor to tumor and can be influenced by
factors such as the tumor's blood supply, the presence of hormones or
growth factors, and the immune response to the tumor.

33
The process of primary tumor growth involves a complex interplay of
cellular and molecular events, including alterations in signaling pathways,
changes in gene expression, and the development of new blood vessels to
supply nutrients and oxygen to the growing tumor. One critical aspect of
tumor growth is the ability of cancer cells to evade the normal mechanisms
that regulate cell growth and division. This evasion can occur through
numerous mechanisms, including mutations in genes that regulate cell cycle
progression, the loss of tumor suppressor genes, and alterations in signaling
pathways that control cell survival and proliferation.
In addition to these intrinsic factors, the growth of the primary tumor can
also be influenced by the surrounding microenvironment. Tumor cells can
alter their surrounding environment, releasing molecules that promote
angiogenesis, recruiting immune cells to the site of the tumor, and
modifying the extracellular matrix to facilitate invasion and migration.
Additionally, tumor-associated fibroblasts and immune cells can secrete
factors that promote tumor growth and survival.As the primary tumor
continues to grow, it can eventually invade nearby tissues and organs. The
ability of cancer cells to invade and migrate is influenced by numerous
factors, including alterations in signaling pathways that regulate cell
motility and adhesion, changes in gene expression, and modifications of the
extracellular matrix. Cancer cells can also secrete enzymes that degrade the
extracellular matrix, allowing them to migrate through tissues and invade
adjacent structures. the growth of the primary tumor is a complex process
that involves numerous genetic, epigenetic, and environmental factors.
Despite our growing understanding of the molecular and cellular
mechanisms that drive tumor growth, there is still much that we do not know
about this process. By better understanding the factors that influence
primary tumor growth, researchers may be able to develop new treatments
that target these processes and help to prevent the spread of cancer to other
parts of the body

34
FIGURE:06

35
 CHAPTER 4
AVOIDANCE OF CELL DEALTH

4.1 APOPTOSIS
Apoptosis, also known as programmed cell death, is a fundamental process
in multicellular organisms that plays a critical role in development,
homeostasis, and disease. The term "apoptosis" was first coined in 1972 by
Kerr, Wyllie, and Currie to describe a distinctive form of cell death that was
different from necrosis. Since then, numerous studies have identified the
molecular and cellular mechanisms that regulate apoptosis, leading to a
deeper understanding of this process and its role in health and disease.
Overview of Apoptosis:
Apoptosis is a highly regulated form of cell death that is characterized by
distinct morphological changes, including chromatin condensation, nuclear
fragmentation, and formation of apoptotic bodies. These changes are
accompanied by biochemical alterations, including activation of caspases,
cleavage of DNA, and externalization of phosphatidylserine. Apoptosis can
be triggered by a variety of stimuli, including developmental cues, DNA
damage, oxidative stress, and activation of death receptors.
The regulation of apoptosis is a complex process that involves a network of
signaling pathways and molecular interactions. In general, apoptotic
signaling can be divided into two main pathways: the intrinsic pathway and
the extrinsic pathway. The intrinsic pathway is activated by internal stimuli,
such as DNA damage or cellular stress, while the extrinsic pathway is
triggered by external signals, such as cytokines or death ligands.
The Intrinsic Pathway:
The intrinsic pathway of apoptosis is regulated by the Bcl-2 family of
proteins, which are located in the mitochondria and regulate the release of
cytochrome c. The Bcl-2 family is composed of both pro-apoptotic and anti-
apoptotic members. The pro-apoptotic members, such as Bax and Bak,
promote the release of cytochrome c from the mitochondria, while the anti-

36
apoptotic members, such as Bcl-2 and Bcl-XL, prevent cytochrome c release
and promote cell survival.
The release of cytochrome c from the mitochondria leads to the activation
of caspases, a family of cysteine proteases that cleave specific substrates
and ultimately lead to the execution of apoptosis. The activation of caspases
occurs through a complex cascade of events that involves the formation of
the apoptosome, a multimeric complex composed of cytochrome c, Apaf-1,
and caspase-9.
The Extrinsic Pathway:
The extrinsic pathway of apoptosis is initiated by the binding of death
ligands, such as Fas ligand or tumor necrosis factor-alpha (TNF-alpha), to
death receptors on the cell surface. The binding of these ligands leads to the
recruitment of adapter proteins, such as FADD, which in turn recruit and
activate caspase-8. The activation of caspase-8 leads to the cleavage of
downstream substrates and ultimately to the execution of apoptosis.
Regulation of Apoptosis:
The regulation of apoptosis is a complex process that involves a variety of
factors, including signaling pathways, post-translational modifications, and
protein-protein interactions. In addition to the Bcl-2 family, numerous other
proteins have been identified that regulate apoptosis, including the IAP
family of proteins, which inhibit caspase activity, and the p53 tumor
suppressor, which can promote apoptosis in response to DNA damage.
Apoptosis in Development:
Apoptosis plays a critical role in development, helping to shape tissues and
eliminate unwanted cells. During development, apoptosis occurs in a highly
regulated manner and is tightly controlled by a variety of signaling pathways
and molecular interactions. For example, in the development of the nervous
system, apoptosis plays a critical role in eliminating excess neurons and
shaping
Mechanisms of Apoptosis:
Apoptosis is a highly regulated process that is triggered by a variety of
signals, both internal and external to the cell. These signals can activate a
number of different intracellular pathways that ultimately converge on a

37
common set of molecular events that result in cell death. The key events that
occur during apoptosis can be grouped into three main stages: initiation,
execution, and clearance.

Initiation:
Apoptosis can be initiated by a variety of signals, including oxidative stress,
DNA damage, growth factor deprivation, and cytokine signaling. These
signals can activate a number of different intracellular pathways, including
the intrinsic and extrinsic pathways.
The intrinsic pathway is initiated by internal signals, such as DNA damage,
that lead to the release of pro-apoptotic proteins from the mitochondria.
These proteins, including cytochrome c, then activate a cascade of proteases
called caspases, which ultimately lead to cell death.
The extrinsic pathway, on the other hand, is initiated by external signals,
such as the binding of death ligands to their corresponding death receptors
on the cell surface. This binding activates a series of intracellular signaling
pathways that ultimately lead to caspase activation and cell death.
Execution:
Once initiated, the apoptotic pathway proceeds through a series of molecular
events that ultimately lead to the dismantling of the cell. The key events that
occur during the execution phase of apoptosis include caspase activation,
DNA fragmentation, cytoskeletal disassembly, and phagocytosis of
apoptotic bodies.
Caspases are a family of cysteine proteases that play a central role in the
execution of apoptosis. There are two types of caspases: initiator caspases
and effector caspases. Initiator caspases, such as caspase-8 and caspase-9,
are activated early in the apoptotic process and then go on to activate the
effector caspases, such as caspase-3 and caspase-7, which are responsible
for the dismantling of the cell.
DNA fragmentation is another key event that occurs during apoptosis. This
fragmentation is mediated by endonucleases, which cleave the DNA into
fragments of approximately 200 base pairs. These fragments are then

38
packaged into apoptotic bodies, which are subsequently engulfed and
degraded by neighboring cells.
Cytoskeletal disassembly is also a critical event in the execution of
apoptosis. This disassembly is mediated by a number of different
mechanisms, including the activation of caspases and the disruption of actin
filaments and microtubules. The disassembly of the cytoskeleton ultimately
leads to the formation of apoptotic bodies.

Clearance:
The final stage of apoptosis is clearance, which involves the phagocytosis
and removal of apoptotic bodies by neighboring cells. This clearance
process is critical to the maintenance of tissue homeostasis and the
prevention of inflammation and tissue damage.
The phagocytosis of apoptotic bodies is mediated by a number of different
mechanisms, including recognition of apoptotic cells by phagocytes,
binding of apoptotic cells to phagocytes, and engulfment of apoptotic cells
by phagocytes. Once engulfed, apoptotic bodies are degraded and their
contents recycled or eliminated.

39
 FIGURE:07
4.2 OCCURANCE OF APOPTOSIS
Apoptosis is a common occurrence in multicellular organisms and is a vital
process for maintaining proper cellular homeostasis. It plays a critical role
in development and tissue turnover, as well as in the removal of damaged or
potentially harmful cells. Apoptosis occurs in response to various internal
and external signals, including DNA damage, oxidative stress, and the
presence of viral or bacterial infections.
During development, apoptosis is essential for sculpting and shaping organs
and tissues. It is involved in the separation of fingers and toes, the formation
of the neural tube, and the maturation of the immune system. In addition,
apoptosis plays a key role in tissue turnover and renewal throughout life,

40
particularly in rapidly dividing tissues such as the skin and the lining of the
digestive tract.
In healthy cells, apoptosis is tightly regulated to prevent unnecessary cell
death. The process is initiated by a variety of signals, including growth
factor withdrawal, DNA damage, and activation of pro-apoptotic proteins.
These signals activate a cascade of intracellular events that ultimately lead
to the activation of a family of cysteine proteases called caspases, which
carry out the actual destruction of the cell.
However, apoptosis can also occur in response to a variety of pathological
conditions, including cancer, neurodegenerative diseases, and autoimmune
disorders. In these cases, apoptosis can either be excessive or insufficient,
leading to either too much or too little cell death.
In cancer, for example, mutations in genes involved in the regulation of
apoptosis can lead to the accumulation of cells that should have been
eliminated. This can result in the formation of tumors, as well as resistance
to chemotherapy and radiation therapy, which often work by inducing
apoptosis in cancer cells.
In neurodegenerative diseases such as Alzheimer's and Parkinson's, the
death of specific neurons is a hallmark of the disease. In these cases,
apoptosis may be triggered by abnormal protein aggregates, oxidative stress,
or other pathological processes. Similarly, in autoimmune diseases, such as
lupus and rheumatoid arthritis, apoptosis may be triggered by the presence
of autoantibodies that recognize and bind to self-antigens on the surface of
cells, leading to their destruction.The occurrence of apoptosis is tightly
regulated and plays a crucial role in maintaining cellular homeostasis in
healthy individuals. However, when dysregulated, it can contribute to the
pathogenesis of a variety of diseases, highlighting the importance of
understanding the mechanisms that control apoptosis in health and disease.

41
4.3 DIAGNOSIS AND STAGES
Cancer is a group of diseases that involve abnormal growth of cells, which can
invade and spread to other parts of the body. It is a major public health concern,
affecting millions of people worldwide, and is one of the leading causes of death.
Diagnosing cancer involves a combination of medical history, physical
examination, imaging tests, and laboratory tests. The goal is to identify cancer at
an early stage when it is more likely to be treatable.
Medical History and Physical Examination
The first step in diagnosing cancer is taking a thorough medical history and
conducting a physical examination. The doctor will ask about symptoms, risk
factors, and family history of cancer. They will also perform a physical exam to
look for any signs of cancer, such as lumps, abnormal moles, or enlarged lymph
nodes.
Imaging Tests
Imaging tests are used to produce pictures of the inside of the body to help
identify cancerous tumors. Common imaging tests include:
X-rays – (This test uses electromagnetic radiation to produce images of bones
and some organs)
X-ray (short for X-radiation) refers to a form of electromagnetic radiation that
has higher energy and shorter wavelength than visible light. X-rays have the
ability to pass through various materials, including body tissues, and produce an
image on a photographic film or digital detector. This property makes X-rays
valuable in medical imaging, where they are commonly used to visualize the
internal structures of the body.
In medical applications, X-rays are used for diagnostic purposes to identify and
diagnose various conditions. For example, they can be used to detect bone
fractures, tumors, infections, and lung diseases. During an X-ray procedure, a
patient is positioned between an X-ray machine and a specialized film or detector.
The X-ray machine emits a controlled dose of radiation that passes through the
body. The X-rays that are not absorbed by the body's tissues strike the film or
detector, producing an image that can be examined by a radiologist.
X- rays are also used in other fields besides medicine. For instance, they are
employed in airport security systems to scan luggage and detect any prohibited
items. X-ray technology is also utilized in industrial applications, such as
inspecting the quality of welds or examining the internal components of

42
manufactured products.It's worth noting that X-rays are a type of ionizing
radiation, meaning they can potentially damage living tissues and cells if exposed
to high doses or over prolonged periods. Therefore, appropriate precautions are
taken to ensure the safety of both patients and medical personnel during X-ray
procedures. Lead aprons and other protective measures are used to minimize
radiation exposure. The benefits of X-ray imaging typically outweigh the risks
when used judiciously and with proper safety measures

CT scans – ( This test uses a combination of X-rays and computer technology

to create detailed images of the body )
A CT scan, also known as a computed tomography scan or CAT scan, is a medical
imaging procedure that uses a combination of X-rays and computer technology
to create detailed cross-sectional images of the body. CT scans provide more
detailed information than traditional X-rays and can visualize internal structures,
organs, and tissues from different angles.
During a CT scan, the patient lies on a table that moves into a doughnut-shaped
machine called a CT scanner. The scanner consists of an X-ray tube that rotates
around the patient, emitting a series of X-ray beams. Detectors on the opposite
side of the scanner measure the amount of radiation that passes through the body
from different angles.The collected data is processed by a computer, which
generates cross-sectional images or "slices" of the body. These images can be
further reconstructed into 3D representations for a more comprehensive view. CT
scans can provide detailed information about bones, organs, blood vessels, and
soft tissues, making them valuable in diagnosing a wide range of medical
conditions.
CT scans are commonly used to:
1. Detect and diagnose various conditions, such as tumors, infections, and
injuries.
2. Assess the extent of trauma or internal injuries after accidents.
3. Guide medical procedures, such as biopsies or needle aspirations.
4. Monitor the effectiveness of ongoing treatments, such as cancer therapy.
Plan radiation therapy and surgical procedures.
CT scans involve exposure to ionizing radiation, similar to X-rays. However,
modern CT scanners are designed to minimize radiation exposure while obtaining
high-quality images. Radiology technologists and radiologists take precautions to

43
ensure that the benefits of the scan outweigh the potential risks associated with
radiation exposure.
It's important to note that CT scans require a medical prescription and should be
performed under the guidance of a healthcare professional. The specific
procedure and preparation instructions may vary depending on the area of the
body being scanned and the purpose of the examination.

MRI – (This test uses a magnetic field and radio waves to create detailed
images of the body).
An MRI scan, or magnetic resonance imaging scan, is a non-invasive medical
imaging technique that uses a combination of strong magnetic fields and radio
waves to create detailed images of the internal structures of the body. MRI
provides highly detailed images of soft tissues, organs, muscles, and other
structures, allowing healthcare professionals to diagnose and monitor various
medical conditions.
During an MRI scan, the patient lies on a movable table that is inserted into a
large, cylindrical machine called an MRI scanner. The scanner contains a
powerful magnet that produces a magnetic field around the patient's body. Radio
waves are then emitted and received by the scanner, causing the body's atoms to
emit signals. These signals are detected by the scanner and processed by a
computer to create detailed, cross-sectional images of the body.
MRI scans offer several advantages:
1. Superior soft tissue visualization: MRI provides exceptional detail of soft
tissues, making it useful for identifying abnormalities in organs, muscles,
ligaments, tendons, and the central nervous system.
2. Multi-planar imaging: MRI can produce images in various planes (sagittal,
coronal, and axial), allowing for a comprehensive evaluation of anatomical
structures from different angles.
3. Non-invasive and radiation-free: Unlike X-rays and CT scans, MRI does
not use ionizing radiation, making it a safe imaging option for most
patients, including pregnant women and children.
4. Contrast-enhanced imaging: In some cases, a contrast agent may be
administered intravenously to enhance the visibility of certain tissues or
blood vessels, aiding in the diagnosis of specific conditions.
5. Functional imaging: Advanced MRI techniques, such as functional MRI
(fMRI), can assess brain activity and help map neural connections, making

44
 them valuable in studying brain function and diagnosing neurological
disorders.
MRI scans are commonly used to diagnose and monitor various medical
conditions, including but not limited to:
1. Brain and spinal cord disorders (e.g., tumors, multiple sclerosis)
2. Musculoskeletal injuries (e.g., torn ligaments, herniated discs)
3. Joint abnormalities (e.g., osteoarthritis, cartilage damage)
4. Abdominal and pelvic conditions (e.g., liver disease, pelvic tumors)
5. Cardiovascular diseases (e.g., heart abnormalities, blood vessel blockages)
Breast and prostate cancer detection and staging
It's important to note that some individuals may not be suitable candidates for an
MRI scan due to certain conditions or devices in their body (e.g., pacemakers,
cochlear implants, metallic implants). Additionally, MRI scans require
cooperation from the patient, as they involve lying still for an extended period
inside a confined space, which can be challenging for individuals with
claustrophobia. Open MRI scanners or sedation options may be available in such
cases.MRI scans are typically ordered by a healthcare professional and should be
performed under their guidance. Preparation instructions may vary depending on
the specific type of MRI scan being conducted and the area of the body being
examined.

PET scans –( This test uses a small amount of radioactive material to produce
images of the body and detect areas of abnormal activity, such as cancer
cells).
A PET scan, or positron emission tomography scan, is a medical imaging
technique that provides information about the metabolic activity of tissues and
organs in the body. Unlike other imaging modalities such as X-rays or MRI,
which primarily show anatomical structures, PET scans focus on the function of
tissues at a molecular level.
During a PET scan, a small amount of a radioactive substance known as a
radiotracer is injected into the patient's bloodstream. The radiotracer is typically
a compound that is similar to glucose (sugar) but tagged with a radioactive atom.
Once inside the body, the radiotracer is absorbed by organs and tissues and
undergoes radioactive decay. As it decays, it emits positrons (positively charged
particles), which collide with electrons in the body, resulting in the emission of
gamma rays.

45
Detectors surrounding the patient's body detect the gamma rays and relay the
information to a computer, which creates detailed 3D images of the metabolic
activity within the body. The images generated by a PET scan can show areas of
high metabolic activity (where the radiotracer has accumulated) and areas of low
activity.
PET scans have several applications in medicine, including:
1. Cancer detection and staging: PET scans can detect abnormal metabolic
activity, helping identify cancerous cells, determine the extent of cancer
spread, and assess treatment response.
2. Brain disorders: PET scans are used to evaluate brain function, detect
abnormalities in conditions such as Alzheimer's disease, epilepsy, and other
neurological disorders.
3. Heart disease: PET scans can assess blood flow to the heart, evaluate heart
function, and identify areas of damaged heart tissue.
4. Evaluation of other diseases: PET scans can be used to assess various
conditions such as infections, inflammation, and certain types of cardiac
and neurological diseases.
PET scans are often combined with CT scans to provide both functional and
anatomical information. This combined imaging technique is called PET/CT,
where the PET scan highlights areas of abnormal metabolic activity, while the CT
scan provides precise anatomical localization.It's important to note that PET scans
involve the use of radiation due to the radioactive tracer. However, the amount of
radiation exposure is generally considered safe and well within acceptable limits.
The radiotracer used in PET scans typically has a short half-life, meaning it
decays quickly and is eliminated from the body relatively fast.
PET scans require a medical prescription and should be performed under the
guidance of a healthcare professional. The specific preparation instructions may
vary depending on the purpose of the scan and the area of the body being
examined.
Laboratory Tests
Laboratory oncological tests refer to a range of diagnostic tests and procedures
performed in a laboratory setting to aid in the diagnosis, prognosis, and
monitoring of cancer. These tests are typically ordered by oncologists or other
healthcare professionals specializing in the treatment of cancer.
Here are some commonly performed laboratory tests in oncology:

46
Tumor Markers:
Tumor markers are substances produced by cancer cells or normal cells in
response to cancer. They can be detected in blood, urine, or tissue samples.
Examples of tumor markers include prostate-specific antigen (PSA) for prostate
cancer, carcinoembryonic antigen (CEA) for colorectal and other cancers, and
CA-125 for ovarian cancer. Tumor markers are used to screen for certain cancers,
assess treatment response, and monitor disease progression.
Genetic Testing:
Genetic testing analyzes DNA or RNA to identify specific genetic mutations or
alterations that are associated with an increased risk of developing cancer or
affecting treatment options. These tests can include tests for hereditary cancer
syndromes (e.g., BRCA1 and BRCA2 mutations) or genomic profiling of tumors
to guide targeted therapy selection.
Histopathology:
Histopathology involves the microscopic examination of tissue samples obtained
through biopsy or surgery. Pathologists study the tissue samples to determine the
presence of cancer cells, their type, grade, and other characteristics. This
information is crucial for cancer diagnosis, staging, and treatment planning.
Cytogenetics:
Cytogenetic tests analyze the chromosomes within cells to detect chromosomal
abnormalities, such as translocations, deletions, or amplifications. These
abnormalities can provide important diagnostic and prognostic information in
various types of cancer, including leukemias and lymphomas.
Flow Cytometry:
Flow cytometry is a technique that analyzes the characteristics of individual cells
in a sample, such as their size, shape, and protein expression. In oncology, flow
cytometry is commonly used to diagnose and classify blood cancers, including
leukemia and lymphoma, based on the specific markers expressed on the surface
of cells.
Molecular Profiling:
Molecular profiling assesses specific molecular alterations within cancer cells,
such as mutations, gene fusions, or changes in gene expression. This information
can help guide treatment decisions, including the use of targeted therapies or
immunotherapies.

47
These are just a few examples of laboratory tests used in oncology. The specific
tests ordered for an individual patient will depend on factors such as the type of
cancer suspected or diagnosed, the stage of the disease, and the goals of the testing
as determined by the healthcare provider. The results of these tests are important
in developing an accurate diagnosis and tailoring an appropriate treatment plan
for each patient.

Biopsy – (This involves taking a sample of tissue from a suspected tumor to

be examined under a microscope for signs of cancer.)
A biopsy is a medical procedure performed in oncology to obtain a tissue sample
from a suspicious area or tumor for further examination and diagnosis. It involves
the removal of a small amount of tissue, cells, or fluid from the body, which is
then examined under a microscope by a pathologist to determine if cancer or other
abnormalities are present.
There are different types of biopsies used in oncology, depending on the location
and nature of the suspected cancer:
Needle Biopsy:
This type of biopsy involves inserting a thin needle into the tumor or affected area
to obtain a tissue sample. There are different types of needle biopsies, including:
Fine-needle aspiration (FNA):
Uses a thin needle to extract cells or fluid from a lump or suspicious area.
Core needle biopsy:
Uses a slightly larger needle to remove a small cylinder of tissue from the tumor.
Vacuum-assisted biopsy:
Utilizes a needle with a vacuum-powered device to collect multiple tissue
samples with a single insertion.
Surgical Biopsy:
In some cases, a surgical biopsy may be necessary to obtain a larger tissue sample
or if the tumor is deep within the body. Surgical biopsies can be open biopsies,
where a surgeon makes an incision to access the tumor, or minimally invasive
procedures, such as laparoscopic or endoscopic biopsies, which use small
incisions and specialized tools to remove tissue samples.

48
Excisional Biopsy:
In certain cases, when a small tumor is suspected, the entire tumor may be
removed during the biopsy procedure. This is known as an excisional biopsy and
can serve both diagnostic and therapeutic purposes.
The collected tissue samples are sent to a pathology laboratory, where a
pathologist examines them under a microscope. The pathologist looks for signs
of cancer cells, their characteristics, and other features that help determine the
type, grade, and stage of the cancer. This information is crucial in guiding
treatment decisions and developing an appropriate treatment plan.Biopsies are
typically performed under local anesthesia, but in some cases, general anesthesia
may be used. The specific procedure and recovery process depend on the type
and location of the biopsy performed.
It's important to note that biopsies are not always necessary for all suspected
cancer cases, especially if the diagnosis can be made through non-invasive
imaging techniques or if the tumor is easily accessible for complete surgical
removal. The decision to perform a biopsy is made based on individual patient
factors and the judgment of the healthcare team involved in the patient's care.
Blood tests - These tests can detect certain substances in the blood that may be
associated with cancer, such as tumor markers.
Urine tests - These tests can detect certain substances in the urine that may be
associated with cancer.
Genetic tests - These tests can detect mutations in genes that are associated with
an increased risk of developing certain types of cancer.

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STAGING
Once a diagnosis of cancer has been made, the next step is to determine the stage
of the cancer. Staging refers to the extent of the cancer and how far it has spread.
The stage of cancer is important in determining the best treatment options and the
prognosis (outlook) for the patient.
The stage of cancer is determined by a combination of imaging tests and other
diagnostic tests, such as biopsies. The stages of cancer are generally classified as
follows:
Stage 0 - Cancer is in its earliest stage and has not spread beyond the site
where it started.
Stage 0 cancer, also known as carcinoma in situ, refers to a very early stage of
cancer where abnormal cells are present only in the layer of cells where they first
formed and have not spread to nearby tissues or other parts of the body.
Stage 0 cancer is typically detected through screening tests, such as
mammograms for breast cancer or colonoscopies for colon cancer, before any
symptoms are present. Treatment for stage 0 cancer may involve surgery to
remove the abnormal cells or close monitoring to watch for any changes in the
cells.
The prognosis for stage 0 cancer is generally very good, as the cancer is localized
and has not spread to other parts of the body. However, if left untreated, stage 0
cancer can progress to more advanced stages of cancer, which may be more
difficult to treat.
It is important to follow recommended screening guidelines and to discuss any
concerns about cancer with a healthcare professional. Early detection and
treatment can greatly increase the chances of a successful outcome and improve
overall quality of life.

Stage I - Cancer is localized and has not spread to nearby lymph nodes or
other parts of the body.
Stage I cancer is an early stage of cancer that has not yet spread to nearby tissues
or lymph nodes. It is typically smaller in size than later stages of cancer and has
a good prognosis when detected early.

50
Types of Stage I Cancer
Stage I cancer can occur in various parts of the body, including the breast, lung,
colon, skin, prostate, and others. Each type of cancer has its own set of symptoms,
diagnostic tests, and treatment options.
Breast Cancer: In stage I breast cancer, the cancer is typically small and has not
spread to nearby lymph nodes. Symptoms may include a lump in the breast,
changes in the shape or size of the breast, or changes in the skin over the breast.
Lung Cancer: Stage I lung cancer refers to cancer that is confined to the lung
and has not spread to other parts of the body. Symptoms may include coughing,
shortness of breath, chest pain, or coughing up blood.
Colon Cancer: In stage I colon cancer, the cancer has not yet spread beyond the
inner lining of the colon. Symptoms may include changes in bowel habits, blood
in the stool, abdominal pain, or unexplained weight loss.
Skin Cancer: Stage I skin cancer refers to cancer that is confined to the top layer
of the skin and has not spread to nearby lymph nodes or other parts of the body.
Symptoms may include a change in the appearance of a mole or other skin lesion,
or a new growth on the skin.
Prostate Cancer: Stage I prostate cancer refers to cancer that is small and has
not spread outside of the prostate gland. Symptoms may include difficulty
urinating, blood in the urine or semen, or erectile dysfunction.
Diagnosis of Stage I Cancer
Diagnosis of stage I cancer typically involves a combination of imaging tests,
laboratory tests, and biopsies. The goal is to determine the type and stage of
cancer and to develop a treatment plan tailored to the patient's individual needs.
Imaging Tests: Imaging tests may include X-rays, CT scans, MRI scans, PET
scans, or ultrasound tests. These tests can help identify the location and size of
the cancer and whether it has spread to nearby tissues or lymph nodes.
Laboratory Tests: Laboratory tests may include blood tests, urine tests, or other
tests to detect specific substances in the body that may be associated with cancer.
Biopsy: A biopsy involves taking a small sample of tissue from the area suspected
of being cancerous and examining it under a microscope. This can help confirm
the diagnosis of cancer and provide information on the type and stage of the
cancer.

51
Staging of Stage I Cancer
Staging of cancer refers to the extent of the cancer and how far it has spread. In
stage I cancer, the cancer is typically localized to a specific area and has not
spread to nearby tissues or lymph nodes.

Stage II - Cancer has grown larger and may have spread to nearby lymph
nodes, but has not spread to other parts of the body.

Stage II cancer is an early stage of cancer that has grown beyond the initial site
and may have spread to nearby tissues or lymph nodes. It is typically larger in
size than stage I cancer and may have a slightly lower prognosis, but early
detection and treatment can still lead to successful outcomes.
Types of Stage II Cancer
Stage II cancer can occur in various parts of the body, including the breast, lung,
colon, skin, prostate, and others. Each type of cancer has its own set of symptoms,
diagnostic tests, and treatment options.
Breast Cancer: In stage II breast cancer, the cancer has grown beyond the initial
site and may have spread to nearby lymph nodes. Symptoms may include a lump
in the breast, changes in the shape or size of the breast, or changes in the skin
over the breast.
Lung Cancer: Stage II lung cancer refers to cancer that has grown beyond the
lung and may have spread to nearby lymph nodes. Symptoms may include
coughing, shortness of breath, chest pain, or coughing up blood.
Colon Cancer: In stage II colon cancer, the cancer has grown beyond the inner
lining of the colon and may have spread to nearby lymph nodes. Symptoms may
include changes in bowel habits, blood in the stool, abdominal pain, or
unexplained weight loss.
Skin Cancer: Stage II skin cancer refers to cancer that has grown beyond the top
layer of the skin and may have spread to nearby lymph nodes or other parts of the
body. Symptoms may include a change in the appearance of a mole or other skin
lesion, or a new growth on the skin.
Prostate Cancer: Stage II prostate cancer refers to cancer that has grown beyond
the prostate gland and may have spread to nearby tissues or lymph nodes.

52
Symptoms may include difficulty urinating, blood in the urine or semen, or
erectile dysfunction.
Diagnosis of Stage II Cancer
Diagnosis of stage II cancer typically involves a combination of imaging tests,
laboratory tests, and biopsies. The goal is to determine the type and stage of
cancer and to develop a treatment plan tailored to the patient's individual needs.
Imaging Tests: Imaging tests may include X-rays, CT scans, MRI scans, PET
scans, or ultrasound tests. These tests can help identify the location and size of
the cancer and whether it has spread to nearby tissues or lymph nodes.
Laboratory Tests: Laboratory tests may include blood tests, urine tests, or other
tests to detect specific substances in the body that may be associated with cancer.
Biopsy: A biopsy involves taking a small sample of tissue from the area suspected
of being cancerous and examining it under a microscope. This can help confirm
the diagnosis of cancer and provide information on the type and stage of the
cancer.
Staging of Stage II Cancer
Staging of cancer refers to the extent of the cancer and how far it has spread. In
stage II cancer, the cancer has typically grown beyond the initial site and may
have spread to nearby tissues or lymph nodes.

Stage III - Cancer has spread to nearby lymph nodes and may have grown
into nearby tissues, but has not spread to other parts of the body.
Stage III cancer is an advanced stage of cancer that has spread beyond the initial
site to nearby lymph nodes or other tissues. It is typically larger and more invasive
than stage II cancer, and the prognosis may be less favorable. However, with
proper treatment, many people with stage III cancer can still achieve remission
or long-term survival.
Types of Stage III Cancer
Stage III cancer can occur in various parts of the body, including the breast, lung,
colon, skin, prostate, and others. Each type of cancer has its own set of symptoms,
diagnostic tests, and treatment options.
Breast Cancer: In stage III breast cancer, the cancer has spread to nearby lymph
nodes or other tissues in the breast. Symptoms may include a lump in the breast,
changes in the shape or size of the breast, or changes in the skin over the breast.

53
Lung Cancer: Stage III lung cancer refers to cancer that has spread beyond the
lung and may have affected nearby lymph nodes or other tissues. Symptoms may
include coughing, shortness of breath, chest pain, or coughing up blood.
Colon Cancer: In stage III colon cancer, the cancer has grown through the outer
layers of the colon and may have spread to nearby lymph nodes or other tissues.
Symptoms may include changes in bowel habits, blood in the stool, abdominal
pain, or unexplained weight loss.
Skin Cancer: Stage III skin cancer refers to cancer that has spread to nearby
lymph nodes or other tissues, or has grown beyond the top layer of the skin.
Symptoms may include a change in the appearance of a mole or other skin lesion,
or a new growth on the skin.
Prostate Cancer: Stage III prostate cancer refers to cancer that has spread beyond
the prostate gland and may have affected nearby tissues or lymph nodes.
Symptoms may include difficulty urinating, blood in the urine or semen, or
erectile dysfunction.
Diagnosis of Stage III Cancer
Diagnosis of stage III cancer typically involves a combination of imaging tests,
laboratory tests, and biopsies. The goal is to determine the type and stage of
cancer and to develop a treatment plan tailored to the patient's individual needs.
Imaging Tests: Imaging tests may include X-rays, CT scans, MRI scans, PET
scans, or ultrasound tests. These tests can help identify the location and size of
the cancer and whether it has spread to nearby tissues or lymph nodes.
Laboratory Tests: Laboratory tests may include blood tests, urine tests, or other
tests to detect specific substances in the body that may be associated with cancer.
Biopsy: A biopsy involves taking a small sample of tissue from the area suspected
of being cancerous and examining it under a microscope. This can help confirm
the diagnosis of cancer and provide information on the type and stage of the
cancer.
Staging of Stage III Cancer
Staging of cancer refers to the extent of the cancer and how far it has spread. In
stage III cancer, the cancer has typically spread beyond the initial site to nearby
lymph nodes or other tissues.
The stage of stage III cancer is further subdivided into three subcategories:

54
Stage IIIA: The cancer has spread to nearby lymph nodes, but they are not large
or have not grown into nearby tissues.
Stage IIIB: The cancer has spread to nearby lymph nodes that are larger or have
grown into nearby tissues.
Stage IIIC: The cancer has spread to nearby lymph nodes, as well as other nearby
tissues or organs.

Stage IV - Cancer has spread to other parts of the body, such as the lungs,
liver, or bones.
Stage IV cancer, also known as metastatic cancer, is an advanced stage of cancer
that has spread from the original site to other parts of the body. This type of cancer
is typically considered incurable, but treatment can help manage symptoms,
prolong survival, and improve quality of life.
Types of Stage IV Cancer
Stage IV cancer can occur in various parts of the body, including the breast, lung,
colon, skin, prostate, and others. Each type of cancer has its own set of symptoms,
diagnostic tests, and treatment options.
Breast Cancer: In stage IV breast cancer, the cancer has spread beyond the breast
to other parts of the body, such as the bones, liver, lungs, or brain. Symptoms may
include bone pain, shortness of breath, fatigue, or confusion.
Lung Cancer: Stage IV lung cancer refers to cancer that has spread to distant
sites in the body, such as the brain, bones, or liver. Symptoms may include
coughing, shortness of breath, chest pain, or coughing up blood.
Colon Cancer: In stage IV colon cancer, the cancer has spread to other parts of
the body, such as the liver, lungs, or bones. Symptoms may include changes in
bowel habits, blood in the stool, abdominal pain, or unexplained weight loss.
Skin Cancer: Stage IV skin cancer refers to cancer that has spread to distant sites
in the body, such as the lymph nodes, liver, lungs, or brain. Symptoms may
include a change in the appearance of a mole or other skin lesion, or a new growth
on the skin.
Prostate Cancer: Stage IV prostate cancer refers to cancer that has spread to
other parts of the body, such as the bones, liver, or lungs. Symptoms may include
difficulty urinating, bone pain, or unexplained weight loss.

55
Diagnosis of Stage IV Cancer
Diagnosis of stage IV cancer typically involves a combination of imaging tests,
laboratory tests, and biopsies. The goal is to determine the type and stage of
cancer and to develop a treatment plan tailored to the patient's individual needs.
Imaging Tests: Imaging tests may include X-rays, CT scans, MRI scans, PET
scans, or ultrasound tests. These tests can help identify the location and size of
the cancer and whether it has spread to other parts of the body.
Laboratory Tests: Laboratory tests may include blood tests, urine tests, or other
tests to detect specific substances in the body that may be associated with cancer.
Biopsy: A biopsy involves taking a small sample of tissue from the area suspected
of being cancerous and examining it under a microscope. This can help confirm
the diagnosis of cancer and provide information on the type and stage of the
cancer.
Staging of Stage IV Cancer
Staging of cancer refers to the extent of the cancer and how far it has spread. In
stage IV cancer, the cancer has spread beyond the initial site to other parts of the
body.
The stage of stage IV cancer is further subdivided into three subcategories:
Stage IVA: The cancer has spread to one distant site in the body, such as the liver,
lungs, or bones.
Stage IVB: The cancer has spread to more than one distant site in the body, such
as the liver, lungs, bones, or brain.
Stage IVC: The cancer has spread throughout the body, including to distant sites
in organs such as the liver, lungs, bones, or brain.

56
 CHAPTER 5
TREATMENT
Treatment for conditions related to apoptosis depends on the specific disease
or disorder involved. For example, cancer treatment may involve
chemotherapy or radiation therapy to induce apoptosis in cancer cells, while
treatment for neurodegenerative diseases may focus on preventing
excessive apoptosis in affected neurons. Overall, treatment approaches aim
to restore proper apoptotic regulation and promote overall cellular health.
THERE ARE MAINLY FOUR TYPES OF TREATMENTS ARE
AVAILABLE FOR CANCER
THEY ARE ,
➢ PRECISION MEDICINE
➢ SURGERY
➢ CHEMOTHERAPY
➢ IMMUNOTHERAPY

5.1 PRECISION MEDICINE

Precision medicine is a rapidly growing field that aims to tailor medical
treatments to the unique characteristics of individual patients. In the context
of cancer, precision medicine involves using genomic and other molecular
information to identify specific molecular targets that can be targeted with
drugs or other therapies. This approach holds great promise for improving
cancer treatment outcomes and reducing the burden of cancer worldwide.
The development of precision medicine approaches for cancer is made
possible by advances in genomic sequencing technologies, which have
allowed researchers to identify a wide range of genetic mutations and other
molecular alterations that are associated with cancer development and
progression. By analyzing the DNA of cancer cells, researchers can identify
specific mutations or other genetic alterations that may be driving the
growth and spread of a patient's tumor.

57
One of the most well-known examples of precision medicine in cancer
treatment is the use of targeted therapies. Targeted therapies are drugs that
are designed to inhibit specific molecular targets that are involved in cancer
cell growth and survival. For example, some targeted therapies work by
inhibiting the activity of specific proteins or enzymes that are overactive in
cancer cells, while others work by blocking the signaling pathways that
promote cancer cell growth and survival.
Targeted therapies have shown great promise in the treatment of several
types of cancer, particularly those that are driven by specific genetic
mutations or other molecular alterations. For example, the drug imatinib,
which targets the BCR-ABL protein that is overactive in chronic
myelogenous leukemia, has revolutionized the treatment of this disease,
leading to improved survival rates and better quality of life for patients.
Another approach to precision medicine in cancer treatment involves the
use of immune checkpoint inhibitors. Immune checkpoint inhibitors are
drugs that work by blocking proteins that are involved in the suppression of
the immune response. By blocking these proteins, immune checkpoint
inhibitors can help to unleash the power of the immune system to attack
cancer cells.
Like targeted therapies, immune checkpoint inhibitors have shown great
promise in the treatment of certain types of cancer, particularly those that
are resistant to other forms of treatment. For example, the drug
pembrolizumab has been shown to improve survival in patients with
advanced melanoma and certain types of lung cancer.In addition to targeted
therapies and immune checkpoint inhibitors, precision medicine approaches
for cancer treatment also include the use of molecular profiling to guide
treatment decisions. Molecular profiling involves analyzing the genetic and
molecular characteristics of a patient's tumor to identify specific mutations
or other molecular alterations that may be driving the growth and spread of
the cancer.This information can then be used to select the most appropriate
treatment for the patient, based on the molecular characteristics of their
tumor. For example, a patient with a particular mutation may be more likely
to respond to a targeted therapy that inhibits the activity of the protein
encoded by that mutation.

58
Molecular profiling is becoming increasingly important in the treatment of
cancer, as more and more targeted therapies and other precision medicine
approaches are developed. In addition, advances in genomic sequencing
technologies are making it possible to sequence a patient's tumor more
quickly and accurately than ever before, allowing for more personalized and
effective treatment decisions.
Overall, precision medicine holds great promise for improving cancer
treatment outcomes and reducing the burden of cancer worldwide. By
tailoring treatments to the unique characteristics of individual patients,
precision medicine approaches can help to improve survival rates, reduce
side effects, and improve quality of life for cancer patients. While there is
still much work to be done to fully realize the potential of precision
medicine in cancer treatment, the future looks bright for this exciting and
rapidly evolving field

5.2 SURGERY
Surgery is one of the most common treatment options for cancer and
involves the removal of the cancerous tissue from the body. The main goal
of surgery is to completely remove the cancerous tissue and prevent it from
spreading to other parts of the body. The success of surgery depends on
various factors such as the type and stage of cancer, location of the tumor,
the patient’s overall health, and the surgeon’s experience.
Types of Surgery:
Curative Surgery:
Curative surgery is the primary treatment for cancer and involves the
complete removal of the cancerous tissue. The goal of curative surgery is to
remove the cancerous tissue and prevent it from spreading to other parts of
the body. This type of surgery is usually performed in the early stages of
cancer when the tumor is still localized.
Palliative Surgery:
Palliative surgery is performed to relieve the symptoms of cancer, such as
pain, bleeding, or difficulty breathing, when the cancer has spread to other

59
parts of the body. This type of surgery does not aim to cure the cancer, but
rather to improve the patient’s quality of life.
Preventive Surgery:
Preventive surgery is performed in people who have a high risk of
developing cancer, such as those with a family history of cancer or those
with a genetic predisposition to cancer. This type of surgery aims to remove
the tissue that is at risk of developing cancer and reduce the risk of cancer.
Diagnostic Surgery:
Diagnostic surgery is performed to confirm the presence of cancer and
obtain a tissue sample for analysis. This type of surgery is usually performed
when other diagnostic tests, such as imaging or biopsy, are inconclusive.
Reconstructive Surgery:
Reconstructive surgery is performed after the removal of cancerous tissue
to restore the appearance and function of the affected area. This type of
surgery is commonly used in breast cancer patients who have undergone a
mastectomy.
Risks and Side Effects:
Like any surgical procedure, cancer surgery also carries certain risks and
side effects. Some of the common risks associated with cancer surgery
include bleeding, infection, reaction to anesthesia, and damage to nearby
organs or tissues. Some of the common side effects of cancer surgery
include pain, swelling, and bruising at the site of the incision, fatigue, and
loss of appetite.
Recovery:
The recovery time after cancer surgery varies depending on the type of
surgery and the patient’s overall health. In general, patients are advised to
avoid strenuous physical activity and heavy lifting for several weeks after
surgery. Patients may also be advised to undergo physical therapy to regain
strength and mobility in the affected area. The surgeon will provide specific
instructions on postoperative care, such as wound care and pain
management.

60
Follow-Up Care:
Follow-up care is an essential component of cancer treatment and involves
regular check-ups to monitor the patient’s recovery and detect any signs of
recurrence. The follow-up care plan may include regular physical exams,
imaging tests, and blood tests. The frequency and duration of follow-up care
depend on the type and stage of cancer and the patient’s overall health.
Conclusion:
Surgery plays a vital role in the treatment of cancer and can be curative,
palliative, preventive, diagnostic, or reconstructive. The success of surgery
depends on various factors such as the type and stage of cancer, location of
the tumor, the patient’s overall health, and the surgeon’s experience. Like
any surgical procedure, cancer surgery also carries certain risks and side
effects. Patients should discuss the risks and benefits of surgery with their
healthcare provider and carefully follow the postoperative care plan to
ensure a successful recovery

61
FIGURE:08

62
 5.3 CHEMOTHERAPY

Chemotherapy is a type of cancer treatment that uses powerful drugs to kill

cancer cells or slow down their growth. It is one of the most common and
widely used treatments for cancer. The drugs used in chemotherapy work by
targeting and destroying rapidly dividing cancer cells. However, they can
also affect healthy cells that divide rapidly, such as those in the bone
marrow, gastrointestinal tract, and hair follicles, leading to side effects.
Chemotherapy can be administered in several ways, including intravenously
(through a vein), orally (by mouth), topically (applied to the skin), or
intramuscularly (injected into a muscle). The choice of chemotherapy drugs
and the method of administration depend on several factors, including the
type of cancer, stage of cancer, overall health of the patient, and other
treatments received.
Chemotherapy is used for several purposes in the treatment of cancer,
including:
Curative treatment:
Chemotherapy can be used as the primary treatment for some types of
cancer, such as leukemia, lymphoma, and testicular cancer. In these cases,
chemotherapy can often cure the cancer, especially when combined with
other treatments such as radiation therapy or surgery.
Adjuvant therapy: Adjuvant chemotherapy is given after surgery to kill
any remaining cancer cells and reduce the risk of cancer recurrence. It is
commonly used for breast cancer, colorectal cancer, and lung cancer.
Neoadjuvant therapy: Neoadjuvant chemotherapy is given before surgery
to shrink the tumor and make it easier to remove. This approach is
commonly used for breast cancer, lung cancer, and other types of cancer.
Palliative treatment: Chemotherapy can be used to relieve symptoms of
advanced or metastatic cancer, such as pain, bleeding, or breathing
difficulties.
While chemotherapy can be effective in killing cancer cells, it can also cause
several side effects, including:

63
Nausea and vomiting: Chemotherapy drugs can affect the digestive system,
leading to nausea and vomiting. Anti-nausea medication can be given to
help manage these side effects.
Hair loss: Chemotherapy drugs can cause hair loss, although the severity
and extent of hair loss depend on the type of drug and the dose.
Fatigue: Chemotherapy can cause fatigue, weakness, and a general feeling
of malaise.
Increased risk of infection: Chemotherapy can weaken the immune system,
increasing the risk of infection.
Anemia: Chemotherapy can lower the number of red blood cells, leading to
anemia and fatigue.
Increased risk of bleeding: Chemotherapy can lower the number of
platelets, which are responsible for blood clotting, leading to an increased
risk of bleeding and bruising.
Neuropathy: Some chemotherapy drugs can damage nerves, leading to
numbness, tingling, or weakness in the hands and feet.
Despite these side effects, chemotherapy remains an important and effective
treatment for many types of cancer. Several new drugs and drug
combinations are currently being developed and tested in clinical trials, with
the goal of improving treatment outcomes and reducing side effects.

64
 FIGURE:09

5.4 IMMUNOTHERAPY
Immunotherapy is a type of cancer treatment that aims to harness the body's
own immune system to target and destroy cancer cells. The immune system
is capable of recognizing and eliminating cancer cells, but in some cases,
cancer cells can evade the immune system's detection and destruction.
Immunotherapy works by enhancing the immune system's ability to
recognize and attack cancer cells, thereby improving the body's natural
defense against cancer.
There are several different types of immunotherapy, each with its own
mechanism of action. One type of immunotherapy is monoclonal antibodies,
which are synthetic proteins designed to recognize and bind to specific
proteins on the surface of cancer cells. By binding to these proteins,
monoclonal antibodies can either directly destroy cancer cells or trigger an
immune response that leads to the destruction of cancer cells.
Another type of immunotherapy is checkpoint inhibitors, which are drugs
that target molecules on immune cells that act as "checkpoints" to prevent
the immune system from attacking healthy cells. Cancer cells can
sometimes use these checkpoints to evade the immune system's detection
and destruction. Checkpoint inhibitors work by blocking these checkpoints,
thereby allowing the immune system to recognize and attack cancer cells.

65
Adoptive cell therapy is another type of immunotherapy that involves
removing immune cells from a patient, genetically modifying them to
recognize and attack cancer cells, and then re-infusing them back into the
patient's body. This type of immunotherapy has shown promising results in
the treatment of certain types of cancer, such as leukemia and lymphoma.
Cancer vaccines are another type of immunotherapy that work by
stimulating the immune system to recognize and attack cancer cells. Unlike
traditional vaccines, which are designed to prevent infectious diseases,
cancer vaccines are designed to treat existing cancer by stimulating an
immune response against cancer cells.One of the major advantages of
immunotherapy is its potential for long-term remission and even cure.
Unlike chemotherapy and radiation therapy, which often have significant
side effects and can damage healthy cells along with cancer cells,
immunotherapy targets cancer cells specifically, sparing healthy cells from
damage. Additionally, immunotherapy can be effective in treating cancers
that are resistant to traditional chemotherapy and radiation therapy.
However, immunotherapy is not without its limitations and potential side
effects. Some patients may not respond to immunotherapy, and in some
cases, the immune system may attack healthy cells along with cancer cells,
leading to autoimmune reactions. Additionally, immunotherapy can be
expensive and may require a significant amount of time and resources.,
immunotherapy represents a promising avenue for the treatment of cancer,
and ongoing research is exploring new ways to harness the power of the
immune system to fight cancer. As our understanding of the immune system
and cancer biology continues to advance, it is likely that immunotherapy
will play an increasingly important role in the treatment of cancer

66
FIGURE:10

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These are the some of the research article of Cancer Biology

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 GLOSSARY
➢ Anemia
o below normal levels of erythrocytes (red blood cells) causing a
decrease in the oxygen-carrying capacity of the blood.
➢ Benign
o Not cancerous - not spreading, usually a more mild disease. Non-
malignant.
➢ Bone-Marrow-Transplant
o A procedure in which a section of bone marrow is taken from one
person and transplanted into another. It is used to replace bone
marrow that has been damaged or diseased. It can be a treatment
option in leukemia.

➢ Breast-Cancer
o Breast cancer is the most common type of cancer in women aged
between 35 to 54, incidence has increased such that 1 in 9 women
develop breast cancer in the USA. The most common type of breast
cancer that found in the cells of the breast ducts, other types include
those of the lobes, and inflammatory breast cancer. Between 5 and
10% of breast cancers are known to be hereditary, women with the
defective BRCA1 gene are more likely to develop breast or ovarian
cancer.
➢ Cachexia
o The rapid loss of weight along with fatigue, weakness, and loss of
appetite. This can be a serious problem for patients with advanced
cancer
➢ Immunotherapy
o Treatment of disease by stimulating the body's own immune system.
This is a type of therapy currently being researched as a treatment
for cancer.
➢ Immune-System
o The body system, made up of many organs and cells, that defends
the body against infection, disease, and foreign substances. The
immune system is often stimulated in specific ways to fight cancer
cells.
➢ Hypoplasia
o incomplete / under development of a part of the body.
➢ I-131
o Radioactive Iodine. Iodine is readily uptaken by the thyroid gland,
therefore I-131 may be used in small doses for monitoring thyroid
tissues (thyroid scanning or "I-131 challenge") or in large doses for
treating thyroid cancer ("ablative" I-131).

73
➢ Incidence
o The number of occurrences of a given disease within a population.
Cancer incidence is the number of new cases of cancer diagnosed in
one year. Data on the incidence of cancer are kept by regional and
national/cancer/registries.

➢ Incidence-Rate
o Calculated by dividing the number of new cases of a particular
cancer during a given period of time by the number of people known
to/be/a/risk

➢ Informed-Consent
o is where patients agree to a treatment or randomisation to a clinical
trial having a reasonable understanding of it.
➢ Interferon
o interferons: are Proteins produced by the body with the specific
purpose of regulating cell functions. Interferons are produced in the
laboratory in large quantities, and are sometimes used in the
treatment of certain cancers.
➢ Interleukin-2
o A hormone-like substance produced by the body (certain blood cells,
specifically) that stimulates the growth of blood cells important to
the body's immune system.
➢ Intravenous
o (IV) means into a vein.
➢ Melanoma
o Cancer that begins in the melanocytes and spreads to other skin cells.
Melanoma appears on the skin and looks like a new or changing
mole.

➢ Merkel cell cancer

o Merkel cell cancer (also known as trabecular cancer, or
neuroendocrine cancer of the skin) is a rare type of malignancy
developing on or just beneath the skin. These tumours can develop
at any age, but the peak incidence is between ages 60 - 80. They are
more frequent in white people, the most common sites of diseases
are the face or scalp and other areas of high sun exposure.

➢ Meta-Analysis
o is where data from a number of studies are lumped together in order
to provide evidence for or against a hypothesis.

74
➢ Metastasis
o Where the cancer has spread to other parts of the body beyond
the primary site. Metastatic sites (secondaries) my be regional or
distant from the original tumour.
➢ Monoclonal-Antibody
o An antibody produced in the laboratory that can target specific
antigens (substances that provoke an immune response). They can
be made in large quantities, and are being tested for their use in
cancer/diagnosis/and/treatment.

➢ Morbidity
o Any departure, subjective or objective, from a state of physiological
or psychological well-being. In this sense, sickness, illness, and a
morbid/condition

➢ Mortality
o Looking at the death rates caused by a disease.
o Mortality rate: Calculated by dividing the number of people who
have died of a particular cancer during a given period of time by the
total population at risk.

➢ Multiple-Myeloma
o A cancer of the white blood cells found in the bone marrow.

➢ Myelodysplasia
o Abnormal production and maturation of blood cells; often leading to
deficiency of red cells, white cells and platelets; sometimes leading
to bone marrow failure or leukemia.
➢ Neoplasm
o A new growth of tissue serving no physiological function
➢ Nephrotoxicity
o Some anti cancer drugs may have the side effect of damaging the
kidneys, for example ifosfamide and cisplatin are known to be
nephrotoxic. There are two categories; glomerular and tubular
toxicity relating to the two main areas of the nephron. In studies of
ifosfamide the degree of nephrotoxicity is thought to be related to
the cumulative dose, but there is a good deal of variability between

75
 patients.

➢ Neuroblastoma
o Neuroblastoma occurs most often in babies, young children. It is a
disease in which cancer cells are found in certain nerve cells in the
body, it originates in the adrenal medulla or other sites of
sympathetic nervous system tissue. The most common site is the
abdomen, either in the adrenal glands or around the spinal cord. The
majority of patients present with metastatic disease. Age and stage
are the main prognostic factors. Patients aged under one year at
diagnosis have a more favourable prognosis. Stage 4S are a special
group of patients aged under one year whose neuroblastoma may
undergo spontaneous regression (tumour disappears without
treatment). Also patients aged under one a higher proportion of low
stage patients compared to older patients. There is an excess of males
compared to females, there are a higher proportion of males in
patients with less favourable sites and stage.

➢ Neutropenia
o below normal levels of leukocytes in the blood. Febrile-neutropenia
(neutropenia with fever) is a common toxicity following
chemotherapy.

➢ Neutrophil
o Type of white blood cell; also called a poly; granulocyte; the body's
primary defense against harmful bacteria.
➢ Non-Hodgkin's-Lymphoma
o Any kind of cancer of the lymph tissues other than Hodgkin's disease
➢ Oedema
o abnormally large amounts of fluid in the intercellular tissue spaces.
➢ Oncologist
o A physician who, after extensive training, specializes in cancer
treatment.

➢ Oncology
o A science dealing with the physical, chemical, and biologic
properties and features of cancer, including causes and the disease
process.

76
➢ Osteogenic Sarcoma
o Osteogenic Sarcoma (osteosarcoma) is a bone forming cancer. It is
the most frequent type of bone tumour and is most common between
the agesof 15 to 25. Over 90% of tumours are located in the
metaphysis (the growing ends of the bone), the most common sites
are the long bones of the legs. Most tumours are solitary, around 2%
are multifocal (2 or more bones). It is known that osteosarcoma can
be radiation induced. Osteosarcomas vary greatly in radiological and
pathological features and therefore needs careful diagnosis to
differentiate this from other bone tumours. Most are high grade
intramedullary osteosarcomas, about 5% are low grade lesions,
some are secondary osteosarcomas (for example those caused by
radiationtherapy).

➢ Osteomyelitis
o inflamation of bone - infection
➢ Osteoporosis
o reduction in bone mass = prone to fractures
➢ Paediatric-Oncology
o The branch of medicine which specialises in the study and treatment
of childhood cancer. Treating children requires different
considerations compared with adult oncology, for example potential
treatment side effects may be different to those in adults. Because of
the differences between childhood and adult cancers most children
are treated in specialist paediatric oncology units, in the UK about
80% of children are treated at a UKCCSG centre.

77
 AUTHOR ACHIEVMENTS :

Publications list:
Key publications published by the Author in “INTERNATIONAL JOURNALS”

✓ DOOSLIN MERCY BAI AND S. KOUSIK SARAVANA

(2022); EVALUATION AND QUANTITATIVE ANALYSIS OF BIOACTIVE
COMPOUNDS FROM CHAETOCEROUS CALCITRANS AGAINST
HUMAN PATHOGENS INT. J. OF ADV. RES. 10 (JUN). 309-321] (ISSN 2320-
5407).

✓ DOOSLIN MERCY BAI AND S.KOUSIK SARAVANA (2021);QUALITATIVE

AND MICROBIAL ASSESSMENT OF NANNOCHOLOROPSIS OCCULATA
AGAINST HUMAN PATHOGENS THROUGH GC-MS ANALYSIS IJSRED (
ISSN:2581-7175)

THANK YOU "

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