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RESEARCH INVENTION JOURNAL OF BIOLOGICAL AND APPLIED SCIENCES 3(3):46-50, 2024

©RIJBAS Publications Online ISSN: 1115-6171

Print ISSN: 1597-2879

Precision Oncology: Targeted Therapies for Cancer

Kato Jumba K.
Faculty of Science and Technology Kampala International University Uganda
ABSTRACT
A paradigm change in cancer therapy, precision oncology tailors treatments to a patient's tumor's genetic
features. Precision oncology tackles cancer-causing genetic abnormalities, unlike standard therapies. This
review examines the history, biological foundation, and kinds of targeted medicines that have become
strong alternatives to traditional treatments. Clinical uses have changed due to genetic profiling and
medication development, including monoclonal antibodies and small molecule inhibitors. Although
progress has been achieved, accessibility, medicine resistance, and data integration remain issues.
Precision oncology would use AI, enhance immunotherapy choices, and address socioeconomic
constraints.
Keywords: Precision oncology, Targeted therapies, Genetic mutations, Molecular profiling, Monoclonal
antibodies.

INTRODUCTION
Precision oncology is a revolutionary approach to cancer care that offers personalized, effective, and less
toxic treatments. Traditional methods have limitations, and increasing doses of therapies is often
insufficient. However, targeted therapies have emerged as a promising solution, as they are able to
address specific genetic mutations. Precision oncology tailors treatment options based on individual
molecular alterations, including base substitutions, insertions/deletions, and gene fusions. This approach
improves outcomes by selecting effective treatments or determining the non-suitability of certain
therapies [1]. Early efforts in precision oncology can be traced back to the late 1970s, with two main
approaches: the 'hormonal-targeted' approach for hormone-responsive breast and prostate cancer, and the
'biochemical-targeted' approach for high-dose methotrexate in tumors with impaired dihydrofolate
reductases. These approaches were validated through tests and randomization. The success of hormonal
treatments sparked interest in developing similar approaches for other tumor types. In the 1990s,
precision oncology focused on oncodriver mutations and translocation events, leading to targeted
therapies such as imatinib, gefitinib, lapatinib, and crizotinib. Two additional paradigms have emerged:
exploring tumor molecular profiles for actionable alterations, and using immunotherapy to inhibit
immune checkpoints across all tumor types [2].
DEFINITION AND CONCEPT
Precision oncology is a patient-centered approach to cancer therapy that targets specific characteristics of
an individual patient's disease. It aims to discover actionable genetic alterations in a patient's tumor and
provide medications or recommend clinical trials that would target or leverage that alteration. The term
has been widely adopted by the scientific community and has raised issues beyond science, including the
definition of key terms and the implications of commercialization. Precision oncology emphasizes
disruption, innovation, and collaboration between scientists, bio-pharmaceutical corporations, venture
capitalists, entrepreneurs, and patients. It relies on computational interpretation and data storage to
inform behavioral responses, such as the uptake of precision medicine and DNA profiling risk-reduction.
Precision oncology focuses on creating bio-data banks with tissue samples and clinical treatment data
[3].
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HISTORICAL DEVELOPMENT
Precision oncology has evolved from key discoveries, advancements in testing technologies, and
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significant milestones. The Philadelphia chromosome and the identification of the first oncogene, RAS,
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were crucial breakthroughs. Imatinib, a targeted therapy for CML, paved the way for precision medicine
in treating various cancers. The advent of detection technologies like next-generation sequencing led to
the identification of TP53 and other cancer genes. This enabled the development of targeted therapies
against mutant forms of RAS, BRAF, EGFR, and others. The molecular-guided paradigm was formed
through validation of mutations as drug targets. Precision oncology is the result of collaborative efforts in
basic research, pharmaceuticals, and clinical practice. Keeping up with the rapidly evolving field is
challenging, but the focus will be on the historical first branch and its lessons for other branches [4].
MOLECULAR BASIS OF CANCER
Cancer is a genetic disease that arises from acquired mutations in somatic cells. In the human genome,
there are 20,000-25,000 protein coding genes supported by a large transcriptional regulatory network
comprised of other RNA genes and promoter regulatory elements. Owing to very high fidelity in DNA
replication, the overall mutation rate is estimated as 1-2 mutations per cell division. This low germline
mutation rate translates to ~70 new mutations in any progeny human lymphocytes, on average [5].
Cancer-causing somatic mutations can be acquired at high rates through mechanisms such as faulty DNA
replication, error-checking, repair, cell death, and genome restructuring. Different cancer subtypes have
unique mutation spectrums, with some mutations occurring at higher rates than expected. Alterations can
be categorized as base substitutions, deletions, insertions, copy number variations, or chromosome
structure aberrations. Activation of oncogenes, DNA repair abolishment, and aberrant signal transduction
often converge on the Ras pathway. Additional mutations increase tumor aggressiveness. Telomerase
activation occurs after supporting alterations. Drugs targeting Ras oncogenes are in clinical trials, and
more may be developed for other common mutations in various cancer types [6].
GENETIC MUTATIONS IN CANCER
Cancer is a genetic disease caused by changes in cell genomes. These mutations can be inherited or occur
after conception as somatic mutations. They can involve changes in DNA sequence, copy number
alterations, or structural rearrangements of chromosomes. Mutations can range from small changes to
large deletions or rearrangements. They occur through replicative errors or DNA damage with improper
repair. Cells constantly face risks that can damage their genetic material from internal and environmental
factors [7].
PRINCIPLES OF TARGETED THERAPIES
Practically all therapies developed for cancer are based on the understanding of the disease's fundamentals
- either biology or genetics. Chemotherapies and similarly acting anti-cancer agents are developed to
hinder DNA replication and/or to damage DNA itself by binding to it and/or metabolically controlling
damage repair mechanisms. Old anti-cancer drugs were designed, for instance, to mimic nucleotides and
thus interfere with the replication taking place on DNA. However, any unwanted damage to the genome
can lead to defects eventually causing diseases, including but not limited to diabetes, heart diseases, and
cancer. In turn, new drugs are developed based on understanding the signaling pathways leading to
elevated proliferation and viability [8]. Drugs target proteins involved in aberrantly active signaling
pathways. Monoclonal antibodies can target extracellular receptors activated on tumors, such as
epidermal growth factor receptors or hyperactive FGFR2, mutant p53, and Ras proteins. Fusion proteins
also target aberrantly activated growth factor receptors. Drugs can inhibit soluble extracellular signal
molecules. Herceptin (Trastuzumab) is a monoclonal antibody designed to block extracellular signaling
on Her2 positivity. Monoclonal antibodies can target invading tumor-promoting signals from the
developing vasculature or proteolytic activity on the tumoral extracellular matrix. Antisense
oligonucleotides or RNA interference can interfere with the expression of cancer-causing proteins.
Targeted therapies for cancer mainly focus on kinases but can target any disease-causing proteins,
especially when combined with cytotoxic drugs. Anti-cancer agents are being explored for newly detected
cancers, and there is a search for histo-pathological tests to guide targeted therapy. "Cocktail therapies"
against common mutated signaling pathways may become more prevalent [9].
TYPES OF TARGETED THERAPIES
Targeted therapies control cancer growth by specifically targeting and inhibiting the signals that
promote cancer cell proliferation. This approach is facilitated through the utilization of small molecules
such as BCR-ABL, which directly interact with and modulate genes involved in tumor development and
progression. Additionally, monoclonal antibodies like trastuzumab have the capacity to selectively bind to
specific proteins, thereby inhibiting their function and impeding the growth of cancer cells. These
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targeted therapies have presented notable advancements in the field of oncology, introducing
groundbreaking treatment options for patients. Examples of these significant therapies include rituximab,
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bevacizumab, panitumumab, and cetuximab, each of which offer precise and exceptionally effective
treatment opportunities in the fight against cancer. Through the implementation of these targeted
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therapies, medical professionals have managed to revolutionize cancer treatment, granting individuals
optimal care that greatly improves their prognosis and overall quality of life [10].
CLINICAL APPLICATIONS OF PRECISION ONCOLOGY
Precision oncology has made a significant impact on the cancer treatment landscape over the past two
decades. Earlier, clinicians had limited options for cancer care, usually relying on general approaches like
chemotherapy or radiation for all patients across indications. With advancements in precision medicine,
tumor molecular profiling has enabled the selection of targeted therapies, offering newer approaches and
improved clinical outcomes. Combining these targeted agents with either older approaches or newer
drugs surpassing the early therapeutic window has emerged as a research field with powerful molecular
agents, holding immense promise. Machine learning and artificial intelligence are promising tools that
can provide patient-specific "omic" input data to address nuances of tumors and patients [11]. In recent
years, immune checkpoint inhibitors targeting the PD-1:PD-L1 axis revealed a new immune evasion
mechanism used by tumors. Tumors exploit immunosuppressive mechanisms seen in chronic
inflammation, injury, or infection to escape immune detection. Monoclonal antibodies were developed to
block these molecules, leading to a breakthrough in cancer treatment. These antibodies were approved by
the FDA as monotherapy and were also combined with other treatments. The identification of HLA-
restricted tumor-specific neopeptides, resulting from tumor genome mutation and transcriptomic
processing, is an exciting development. Chemo- or radiation-induced damage increased the presence of
immunogenic/HLA-epitopes, promoting the infiltration of antitumor cytotoxic T-cells. Precision
oncology has reached a steady state, allowing for future developments in target discovery, input data, and
algorithms. Precision oncology can be expanded to various fields with actionable alterations in tumors.
Key issues and challenges, such as cancer-proofing genomes, preventing drug resistance, heterogenic
models, and big data, are also addressed [12-16].
CASE STUDIES
As cancer genomics continues to make significant strides in scientific research, the University of Utah's
esteemed cancer center is dedicated to expanding and amplifying its already robust capabilities in the field
of melanoma research. Recognizing the critical importance of this work, they remain steadfast in their
commitment to investing in necessary infrastructure enhancements, utilizing cutting-edge gene selection
techniques, and fostering collaboration with key stakeholders from diverse backgrounds and expertise. By
pursuing these strategic avenues, the University of Utah's cancer center is actively propelling
advancements in precision oncology, which in turn brings us one step closer to the ultimate triumph over
the challenging adversary that is melanoma [13].
CHALLENGES AND FUTURE DIRECTIONS
Precision oncology has made significant advances over the past decade, resulting in the approval of
numerous targeted agents and their integration into standard oncology practice. However, challenges
remain in the implementation of precision oncology, patient access, and drug development pace, and the
potential risks of overpromising and underdelivering are significant. Furthermore, issues of access and
equity cannot be solved by scientific efforts alone; greater involvement from civic and governmental
leaders is essential. Ongoing efforts to identify and implement the best knowledge translation models to
support equitable patient access should be continued and ramped up globally. Medical science is
undergoing an unprecedented transformation, and the long excitement of the dawn of precision medicine
must now be tempered with pragmatism [14]. Big data and biomedical knowledge are disrupting and
advancing various fields, including biomedicine. They have revolutionized our understanding of disease at
the molecular level, drug discovery, and human physiology. Next-generation sequencing technology is
generating vast genomic data that can be used to create individual tumor portraits. These portraits help
categorize patients into treatment groups for investigational drugs. Precision medicine in cancer has had
success with targeted therapies, but there are challenges in implementing computational and data-driven
approaches. Success stories have come from discovering "simple targets" that can counteract single gene
aberrations, finding secondary therapies to combat drug resistance, and obtaining regulatory approvals
for therapeutic agents [15-18].
CONCLUSION
Precision oncology is revolutionizing cancer treatment by focusing on personalized approaches based on
the molecular characteristics of each patient's tumor. Targeted therapies, such as small molecules and
monoclonal antibodies, have shown promise in controlling cancer growth more effectively and with fewer
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side effects than traditional treatments. Despite the success, challenges such as drug resistance, equitable
access, and integration of big data remain critical hurdles. Moving forward, further advancements in
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genomic technologies, artificial intelligence, and immunotherapy will be essential to enhance treatment
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outcomes and ensure broader access to precision medicine, particularly in underrepresented patient
populations.
REFERENCES
1. Wahida A, Buschhorn L, Fröhling S, Jost PJ, Schneeweiss A, Lichter P, Kurzrock R. The coming
decade in precision oncology: six riddles. Nature Reviews Cancer. 2023 Jan;23(1):43-54.
[HTML]
2. Trimboli RM, Giorgi Rossi P, Battisti NM, Cozzi A, Magni V, Zanardo M, Sardanelli F. Do we
still need breast cancer screening in the era of targeted therapies and precision medicine?.
Insights into Imaging. 2020 Dec;11:1-0. springer.com
3. Plana D, Palmer AC, Sorger PK. Independent drug action in combination therapy: implications
for precision oncology. Cancer discovery. 2022. aacrjournals.org
4. Westermann J, Bullinger L. Precision medicine in myeloid malignancies. Seminars in Cancer
Biology. 2022. [HTML]
5. Robinson PS, Coorens TH, Palles C, Mitchell E, Abascal F, Olafsson S, Lee BC, Lawson AR,
Lee-Six H, Moore L, Sanders MA. Increased somatic mutation burdens in normal human cells
due to defective DNA polymerases. Nature genetics. 2021 Oct;53(10):1434-42. nature.com
6. Elwakeel E, Weigert A. Breast cancer CAFs: spectrum of phenotypes and promising targeting
avenues. International journal of molecular sciences. 2021. mdpi.com
7. Wadowska K, Bil-Lula I, Trembecki Ł, Śliwińska-Mossoń M. Genetic markers in lung cancer
diagnosis: a review. International journal of molecular sciences. 2020 Jun 27;21(13):4569.
mdpi.com
8. Wu SY, Fu T, Jiang YZ, Shao ZM. Natural killer cells in cancer biology and therapy. Molecular
cancer. 2020. springer.com
9. Vultaggio-Poma V, Sarti AC, Di Virgilio F. Extracellular ATP: a feasible target for cancer
therapy. Cells. 2020. mdpi.com
10. Demir Cetinkaya B, Biray Avci C. Molecular perspective on targeted therapy in breast cancer: a
review of current status. Medical Oncology. 2022. springer.com
11. Tsimberidou AM, Fountzilas E, Nikanjam M, Kurzrock R. Review of precision cancer medicine:
Evolution of the treatment paradigm. Cancer treatment reviews. 2020 Jun 1;86:102019.
sciencedirect.com
12. Tang Q, Chen Y, Li X, Long S, Shi Y, Yu Y, Wu W, Han L, Wang S. The role of PD-1/PD-L1
and application of immune-checkpoint inhibitors in human cancers. Frontiers in immunology.
2022 Sep 13;13:964442. frontiersin.org
13. Leachman SA, Hornyak TJ, Barsh G, Bastian BC, Brash DE, Cleaver JE, Cooper CD, D’Orazio
JA, Fujita M, Holmen SL, Indra AK. Melanoma to vitiligo: The melanocyte in biology &
medicine–joint montagna symposium on the biology of skin/panamerican society for pigment
cell research annual meeting. Journal of Investigative Dermatology. 2020 Feb 1;140(2):269-74.
sciencedirect.com
14. Gu W, Meng F, Haag R, Zhong Z. Actively targeted nanomedicines for precision cancer
therapy: Concept, construction, challenges and clinical translation. Journal of controlled release.
2021. core.ac.uk
15. Flory A, Kruglyak KM, Tynan JA, McLennan LM, Rafalko JM, Fiaux PC, Hernandez GE,
Marass F, Nakashe P, Ruiz-Perez CA, Fath DM. Clinical validation of a next-generation
sequencing-based multi-cancer early detection “liquid biopsy” blood test in over 1,000 dogs using
an independent testing set: The CANcer Detection in Dogs (CANDiD) study. PLoS One. 2022
Apr 26;17(4):e0266623. plos.org
16. Emmanuel Ifeanyi Obeagu, Yahye Abdi Ahmed, Getrude Uzoma Obeagu, UO Bunu, OPC Ugwu,
Esther U Alum Biomarkers of breast cancer: Overview. Int. J. Curr. Res. Biol. Med, 2023 (1), 8-16.
17. Emmanuel Ifeanyi Obeagu, Deko Mohamed Omar, Umi Omar Leukaemia burden in Africa. Int. J.
Curr. Res. Biol. Med, 2023,1, 17-22.
18. Esther U Alum, Joseph E Inya, Okechukwu PC Ugwu, Emmanuel I Obeagu, Chinyere Aloke,
Patrick M Aja, Mmesoma G Okpata, Esther C John, Manasseh O Orji, Ozioma Onyema
Ethanolic leaf extract of Datura stramonium attenuates methotrexate-induced biochemical
49

alterations in Wistar Albino rats. RPS Pharmacy and Pharmacology Reports, 2023, 2,(1),1-6.
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CITE AS: Kato Jumba K. (2024). Precision Oncology: Targeted Therapies for Cancer.
RESEARCH INVENTION JOURNAL OF BIOLOGICAL AND APPLIED SCIENCES 3(3):46-
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