Biology of Cancer

Dr. Mahasin A Wadi

 Objectives
• The students must know;
• Definition of Cancer.
• Types of Cancer.
• Difference between Benign and Malignant tumor.
• Classification and Nomenclature of tumor.
• Tumor Markers.
• Angiogenesis.
• Mutation of Normal Genes.
• Cancer and risk factor.
• Treatment of Cancer.
 Cancer
 Cancer
 Derived from Greek word for crab, karkinoma
 Malignant tumor
 Tumor
 Also referred to as a neoplasm—new growth
 Tumor
• The most accepted definition of a tumor is that it is a tissue
overgrowth the law that is independent of governing the remainder
of the body.
• Tumor; referred to swelling= new growth or neoplasm.
• Not all tumor are or neoplasm are cancer.
• Cancer refers to any malignant or neoplasm, and not refer to benign
growth.
 Benign vs. Malignant Tumors
•Benign •Malignant
•Grow slowly •Grow rapidly
•Well-defined capsule •Not encapsulated
•Not invasive •Invasive
•Well differentiated •Poorly differentiated
•Low mitotic index •High mitotic index
•Do not metastasize •Can spread distantly (metastasis)
Cancer Cell
 Tumor Classification and Nomenclature

 Benign tumors
 Named according to the tissues from which they arise, and
include the suffix “–oma
 Lipoma - Tunor of the fat cells.
 Glioma; A glioma is a type of brain tumor that originates from glial cells

 Leiomyoma -Tumor of the smooth muscle of the uterus.

 Chondroma; A chondroma is a benign cartilaginous tumor,

 Classification and Nomenclature

 Malignant tumors
 Named according to the tissues from which they arise
 Malignant epithelial tumors are referred to as carcinomas
 Adenocarcinoma and basal cell carcinoma -. arise from ductal or glandular
epithelium .
 Malignant connective tissue tumors are referred to as sarcomas
 Chondrosarcoma and osteosarcoma
 Classification and Nomenclature
 Cancers of lymphatic tissue are lymphomas
 Cancers of blood-forming cells are leukemias
 Carcinoma in situ (CIS)
 Pre-invasive epithelial malignant tumors of glandular or epithelial
origin that have not broken through the basement membrane or
invaded the surrounding stroma
Classification and Nomenclature
 Tumor Markers
 Tumor cell markers (biological markers) are substances
produced by cancer cells or that are found on plasma cell
membranes, in the blood, CSF, or urine
 Hormones
 Enzymes
 Genes
 Antigens
 Antibodies
 Cells Differentiation
• Cancer cells are defined by two heritable properties;
• Autonomy and anaplasia.
• Autonomy; referred to the cancer cell’s independence from normal
cellular control.
• Anaplasia; is the loss of differentiation = without form.
• Anaplasia is characterize by marked increase in nucleus size.
• Anaplastic cells are of variable size and shape or pleomorphic .
• Cancer cells they less differentiae to perform specific function.
Cancer Cell
 Tumor Markers
 Tumor markers are used to:
 Screen and identify individuals at high risk for cancer
 Diagnose specific types of tumors
 Observe clinical course of cancer
Cancer-Causing Mutations
 Types of Mutated Genes
 Secretion of growth factors (autocrine stimulation)
 Increased growth factor receptors
 Signal from cell-surface receptor is mutated in the “on” position
 Mutation in the ras intracellular signaling protein
 Inactivation of Rb tumor suppressor
 Activation of protein kinases that drive the cell cycle
 Mutation in the p53 gene
Types of Mutated Genes
 Cancer-Causing Mutations
 Cancer is predominantly a disease of aging
 Clonal proliferation or expansion
 Due to a mutation, a cell acquires characteristics that allow it to
have selective advantage over its neighbors
 Increased growth rate or decreased apoptosis
 Multiple mutations are required before cancer can develop
 Angiogenesis

Growth of new vessels

• Advanced cancers can secrete angiogenic factors
Angiogenesis
 Telomeres and Immorality
 Body cells are not immortal and can only divide a limited
number of times
 Telomeres are protective caps on each chromosome and are
held in place by telomerase
 Telomeres become smaller and smaller with each cell
division
 Mutation of Normal Genes
 Point mutations
 Changes in one or a few nucleotide base pairs
 Chromosome translocation
 A piece on one chromosome is transferred to another
 Gene amplification
 Duplication of a small piece of chromosome over and over
 Results in an increased expression of an oncogene
Mutation of Normal Genes
Mutation of Normal Genes
The Genetic Basis of Cancer
Cancer-Causing Mutations
 Mutation of Normal Genes
 Mutation of tumor-suppressor genes
 Allows unregulated cellular growth
 Loss of heterozygosity
 Both chromosome copies of a gene are inactivated
 Gene silencing
 Whole regions of chromosomes are shut off while the same
regions in other cells remain active
 Etiology of Cancer
 Inflammation and Cancer
 Chronic inflammation is an important factor in the
development of cancer
 Cytokine release from inflammatory cells
 Free radicals
 Mutation promotion
 Decreased response to DNA damage
 Genetics and Cancer
 Exposure to mutagens
 If the mutation occurs in somatic cells, it is not passed to progeny
 If the mutation occurs in germline cells, it can be passed to future
generations
 Viruses and Cancer
 Implicated
 Hepatitis B and C viruses
 Epstein-Barr virus (EBV)
 Kaposi sarcoma herpesvirus (KSHV)
 Human papillomavirus (HPV)
 Human T cell leukemia–lymphoma virus (HTLV)
 Bacterial Cause of Cancer
 Helicobacter pylori
 Chronic infections are associated with:
 Peptic ulcer disease
 Stomach carcinoma
 Mucosa-associated lymphoid tissue lymphomas
 Cancer Progression and Metastasis
• Metastasis is the spread of cancer cells from the site of the original
tumor to distant tissue or organs through the body.
• Local spread ; is prerequisite for metastasis and the first step in the
metastatic process.
• Cancer metastasis through veins and lymphatics, first regionally and
then distantly.
• Most cancer cells are not capable of successful metastasis.
 Cancer Progression and Metastasis
• Most cancer cells are not capable of successful metastasis .
• Multiple steps, including invasion, survival the circulation in the
circulation , attachment and growth and induction of angiogenesis at
a favorable distant site are required.
 Phases of Tumor Spread

• Transformation
• Growth
• Local invasion
• Distant metastasis
 Cancer Progression and Metastasis

• Tumor Spread
• Direct invasion of contiguous organs
• Known as local spread
• Metastases to distant organs
• Lymphatics and blood
• Metastases by way of implantation
 Environmental Risk Factors
 Tobacco
 Multipotent carcinogenic mixture
 Linked to cancers of the lung, lower urinary tract, aerodigestive
tract, liver, kidney, pancreas, cervix uteri, and myeloid leukemia
 Environmental Risk Factors
 Ionizing radiation
 Emission from x-rays, radioisotopes, and other radioactive
sources
 Exposure causes cell death, gene mutations, and chromosome
aberrations
 Bystander effects
 Poor gene repair
 Changes in gap junction intercellular communication
 Environmental Risk Factors
 Occupational hazards
 Substantial number of occupational carcinogenic agents
 Asbestos
 Dyes, rubber, paint, explosives, rubber cement, heavy metals, air
pollution, etc.
 Environmental Risk Factors
 Ultraviolet radiation
 Causes basal cell carcinoma, squamous cell carcinoma, and
melanoma
 Principal source is sunlight
 Ultraviolet A (UVA) and ultraviolet B (UVB)
 Promotes skin inflammation and release of free radicals
 Environmental Risk Factors
 Alcohol consumption
 Risk factor for oral cavity, pharynx, hypopharynx, larynx,
esophagus, and liver cancers
 Cigarette/alcohol combination increases a person’s risk
 Environmental Risk Factors
 Obesity
 Correlates with the body mass index (BMI)
 Adipose tissue is active endocrine and metabolic tissue
 In response to endocrine and metabolic signaling, adipose tissue
releases free fatty acids
 Increased free fatty acids gives rise to insulin resistance and causes
chronic hyperinsulinemia
 Correlates with colon, breast, pancreatic, and endometrial cancers
 Environmental Risk Factors
 Sexual reproductive behavior
 Carcinogenic types of human papillomavirus
 High-risk HPV
 Physical activity
 Reduces cancer risk
 Decreases insulin and insulin-like growth factors
 Decreases obesity
 Decreases inflammatory mediators and free radicals
 Increased gut motility
 Clinical Manifestation of Cancer
• Pain: general mechanisms that cause pain associate with cancer
include;
• Pressure, obstruction, invasion of sensitive structure, tissue
destruction, and inflammation.
• Tumor that compress nerve ending create pain.
• Fatigue: is the most frequently reported symptoms of cancer and
cancer treatment.
• The physiologic understanding of fatigue probably includes
mechanisms for decreased muscle contractility.
 Clinical Manifestation of Cancer
• Cachexia: loss of appetite – is one of the most common cause of
death among individual with cancer.
• Anemia: associate with cancer usually occurs because of
malnutrition , long term bleeding and iron deficiency , chemotherapy,
and malignancies in blood forming organs.
• Leukopenia is usually a result of chemotherapy , which is toxic to
bone marrow , or radiation, which kills circulating leukocytes.
• Thrombocytopenia - decrease number of platelets- is usually the
result of chemotherapy or malignancy in the bone marrow.
 Clinical Manifestation of Cancer
• Infection maybe caused by leukopenia, immunosuppression, or
debility associate with advanced disease.
 Cancer Treatment
• Cancer Treatment; cancer is treated with surgery, radiotherapy,
chemotherapy, immunotherapy, and combination of these modalities.
• Surgical therapy is used for non metastatic disease for which cure is possible
by removing tumor.
• Ionizing radiation; causes cell damage , so the goal of radiotherapy is to
damage the tumor without causing excessive toxicity or damage to non
disease structures.
• Combination chemotherapy is the synergistic use of several agents.
• This help decrease single agent drug resistance and reduce harmful effects
on normal cells.
 Cancer Treatment
• The goal of chemotherapy is to eradicate enough tumor cells so the
body’s natural defenses can eradicate remaining cells.
• Immunotherapy; is appropriate for cancer that can not be managed
effectively by chemotherapy or radiation.
• Form of immunotherapy, such as vaccine and biologic response
modifiers , include immunomodulation agents, interferons, antigens,
effectors cells, lymphyokines, and mono clonal antibodies.