Precision Medicine in Cancer Biology: Using Genetic and Molecular Profiling to Personalize Treatment

Precision Medicine in Cancer Biology: Using Genetic and Molecular Profiling to Personalize Treatment

N T Pramathesh Mishra*¹, Ashish Kumar Nirmal¹, Omkar Abadhesh Mishra²,

¹Department of Pharmacology, Hygia College of Pharmacy, Dr A. P. J Abdul Kalam Technical University, Lucknow, UP, 226020

²Epiphany Lifesciences Pvt Ltd, Lucknow, UP, 226021

*Corresponding Author

DOI: https://doi.org/10.51584/IJRIAS.2024.90219

Received: 24 January 2024; Revised: 01 February 2024; Accepted: 05 February 2024; Published: 12 March 2024

ABSTRACT

Precision medicine is an emerging field that aims to provide personalized treatment for cancer patients by utilizing genetic and molecular profiling. By analyzing a patient’s cancer’s genetic and molecular characteristics, doctors can design tailored treatment plans targeting specific mutations or signalling pathways driving tumor growth. This approach can potentially improve patient outcomes by increasing the effectiveness of treatments and reducing the risk of side effects. However, many challenges are associated with implementing precision medicine, including the need for advanced technologies and the high cost of testing and treatment. Despite these obstacles, the promise of precision medicine is driving significant investment and research efforts in the field, and it has the potential to transform the way we treat cancer.

Keywords: Precision Medicine, Cancer Biology, Genetic Profiling, Molecular Profiling, Personalized Treatment

INTRODUCTION

Cancer is a complex and heterogeneous disease, with each patient’s unique genetic and molecular characteristics. Historically, cancer treatment has relied on a one-size-fits-all approach, where patients receive standardized treatments based on the location and stage of their cancer. However, this approach has limitations, as it does not consider the individual differences in tumors and how they respond to treatment. This is where precision medicine comes in, an approach that uses genetic and molecular profiling to tailor treatment to an individual patient’s cancer. Precision medicine can potentially improve patient outcomes by increasing treatment efficacy, reducing the risk of side effects, and reducing the overall cost of treatment. In this article, we will explore the role of genetic and molecular profiling in precision medicine for cancer treatment and the potential benefits and challenges of this approach. [1,2]

GENETIC PROFILING: IDENTIFYING MUTATIONS AND VARIATIONS THAT DRIVE CANCER GROWTH

Genetic profiling is a key component of precision medicine in cancer treatment. By analysing the genetic makeup of a tumor, doctors can identify mutations and variations driving its growth and design targeted treatments that specifically address these abnormalities. Genetic profiling involves analyzing the DNA sequence of the tumor and comparing it to the patient’s normal DNA sequence to identify genetic alterations unique to the tumour.[3]

Many genetic alterations can occur in cancer, including point mutations, insertions, deletions, amplifications, and rearrangements. Some of these alterations can lead to the activation of oncogenes, which promote cell growth and division. In contrast, others can result in the inactivation of tumour suppressor genes, which normally help to prevent cancer.[4]

In recent years, technological advancements have made genetic profiling more accessible and affordable, allowing doctors to incorporate this approach into routine cancer care. Genetic profiling can help identify patients likely to benefit from targeted therapies, drugs designed to target the genetic alterations that are specifically driving tumor growth. This approach can improve treatment efficacy and reduce the risk of side effects compared to traditional chemotherapy, which targets both cancerous and healthy cells. [4,5] Overall, genetic profiling is an important tool in precision medicine, as it allows doctors to understand better the unique genetic characteristics of a patient’s tumor and tailor treatment to address those specific abnormalities.[6]

APPLICATIONS OF GENETIC AND MOLECULAR PROFILING IN CANCER TREATMENT [7-9]

Genetic and molecular profiling has several applications in cancer treatment. Some of the key applications include:

• Identification of molecular targets: Genetic and molecular profiling can help identify specific molecular targets driving the growth and spread of cancer cells. This information can be used to develop targeted therapies targeting these targets.
• Stratification of patients: Genetic and molecular profiling can help stratify patients into different subgroups based on the molecular characteristics of their cancer. This can help identify patients more likely to respond to certain therapies and those who may benefit from alternative treatment options.
• Predictive biomarkers: Genetic and molecular profiling can help identify predictive biomarkers that can be used to predict a patient’s response to a particular therapy. This information can guide treatment decisions and avoid unnecessary treatments that are unlikely to be effective.
• Monitoring treatment response: Genetic and molecular profiling can be used to monitor a patient’s response to treatment over time. This can help identify patients who are not responding to treatment and may benefit from alternative therapies.
• Personalized treatment: Genetic and molecular profiling can help personalize cancer treatment by identifying the most effective therapies for individual patients based on the molecular characteristics of their cancer.

TECHNIQUES USED IN GENETIC AND MOLECULAR PROFILING [10-13]

There are several techniques used in genetic and molecular profiling. Some of the key techniques include:

• DNA sequencing: DNA sequencing determines the precise order of nucleotides (A, C, G, T) in a DNA molecule. DNA sequencing can identify genetic mutations that may drive the growth and spread of cancer cells.
• RNA sequencing: RNA sequencing determines the precise sequence of RNA molecules. RNA sequencing can identify changes in gene expression patterns that may be associated with cancer development and progression.
• Proteomics: Proteomics studies proteins’ structure, function, and cell interactions. Proteomics can be used to identify specific proteins that are overexpressed or mutated in cancer cells.
• Metabolomics: Metabolomics studies the small molecules (metabolites) present in cells. Metabolomics can be used to identify metabolic pathways that may be dysregulated in cancer cells.
• Immunohistochemistry: Immunohistochemistry is a technique that uses antibodies to detect specific proteins in tissue samples. Immunohistochemistry can be used to identify specific proteins that are overexpressed or mutated in cancer cells.
• Fluorescence in situ hybridization (FISH): FISH is a technique that uses fluorescent probes to detect specific DNA sequences in cells. FISH can be used to identify genetic mutations or abnormalities in cancer cells.

CHALLENGES IN IMPLEMENTING PRECISION MEDICINE IN CANCER BIOLOGY [ 14-17]

Implementing precision medicine in cancer biology faces several challenges, including:

• Cost: The cost of genetic and molecular profiling can be high, and the cost of developing and producing targeted therapies can also be significant. This can limit access to these technologies and treatments for some patients and healthcare systems.
• Complexity: Genetic and molecular profiling generates a large amount of data that can be complex and challenging to interpret. This can make it difficult for clinicians to make informed treatment decisions based on the results.
• Limited data: Despite advances in genetic and molecular profiling, there is still limited data on the effectiveness of targeted therapies for many cancer types. This can make it difficult to determine the most appropriate treatment for individual patients.
• Resistance to therapy: Cancer cells can develop resistance to targeted therapies over time, making them less effective. This can require the development of new therapies or combinations of therapies to overcome resistance.
• Privacy concerns: Genetic and molecular profiling involves collecting and storing personal health data, which raises privacy concerns for patients and healthcare providers.
• Accessibility: Precision medicine may not be accessible to all patients due to geographic location, income, and insurance coverage.
• Ethical and legal issues: There are ethical and legal issues surrounding genetic and molecular profiling, such as concerns about genetic discrimination, informed consent, and ownership of genetic data.

ETHICAL AND LEGAL ISSUES SURROUNDING PRECISION MEDICINE IN CANCER BIOLOGY  [18-21]

Precision medicine in cancer biology raises several ethical and legal issues, including:

• Informed consent: Patients must provide informed consent for genetic and molecular profiling and using their health data in research. Patients should be fully informed about the risks and benefits of these technologies and their potential impact on their health and privacy.
• Privacy: Genetic and molecular profiling generates large amounts of personal health data, raising concerns about privacy and data security. Patients should have control over their health data and be informed about how it will be used and protected.
• Genetic discrimination: Patients may face discrimination based on their genetic information, such as denial of health insurance or employment. Laws and policies are in place to protect against genetic discrimination, but they may not be sufficient.
• Ownership of genetic data: Patients and researchers may have competing interests in owning and using genetic data. Patients should be informed about who owns and controls their genetic data and how it will be used.
• Access to precision medicine: Precision medicine may not be accessible to all patients due to geographic location, income, and insurance coverage. Healthcare systems must ensure that all patients have access to the benefits of precision medicine.
• Equity and social justice: Precision medicine can potentially exacerbate health disparities and inequities. Healthcare systems must ensure that precision medicine is implemented equitably and socially justly.
• Regulation and oversight: Precision medicine technologies and therapies require appropriate regulation and oversight to ensure safety, efficacy, and ethical use.

Advantage [22, 23]

1. Personalized treatment: Precision medicine allows for personalized treatment based on a patient’s genetic and molecular profile, leading to more effective and targeted therapies.
2. Improved outcomes: By targeting specific genetic mutations and biomarkers, precision medicine can improve treatment outcomes and potentially extend survival in patients with cancer.
3. Reduced toxicity: Targeted therapies can be more specific and less toxic than traditional chemotherapy, improving patients’ quality of life.
4. Earlier detection: Genetic and molecular profiling can help identify cancer earlier, when it is more treatable, and monitor disease progression more effectively.
5. More efficient clinical trials: Precision medicine can help identify patients most likely to benefit from a specific treatment, leading to more efficient and effective clinical trials.

Disadvantages [24, 25]

1. Cost: The cost of genetic and molecular profiling and targeted therapies can be high, which may limit access to these technologies and treatments for some patients and healthcare systems.
2. Limited data: Despite advances in genetic and molecular profiling, there is still limited data on the effectiveness of targeted therapies for many cancer types.
3. Complexity: Genetic and molecular profiling generates a large amount of data that can be complex and challenging to interpret, making it difficult for clinicians to make informed treatment decisions based on the results.
4. Resistance to therapy: Cancer cells can develop resistance to targeted therapies over time, making them less effective. This can require the development of new therapies or combinations of therapies to overcome resistance.
5. Privacy concerns: Genetic and molecular profiling involves collecting and storing personal health data, which raises privacy concerns for patients and healthcare providers.
6. Accessibility: Precision medicine may not be accessible to all patients due to geographic location, income, and insurance coverage.

FUTURE DIRECTIONS IN PRECISION MEDICINE IN CANCER BIOLOGY [26-27]

• Multi-omics approaches: Combining data from multiple types of genetic and molecular profiling, such as genomics, proteomics, and metabolomics, can provide a more comprehensive understanding of cancer biology and lead to the development of more effective targeted therapies.
• Liquid biopsies: Liquid biopsies, which involve the analysis of circulating tumour cells and cell-free DNA in the blood, offer a less invasive and more frequent method of monitoring tumour progression and response to therapy.
• Artificial intelligence: Artificial intelligence and machine learning can help identify patterns in large amounts of genetic and molecular data and improve the accuracy of cancer diagnosis and treatment decisions.
• Patient-reported outcomes: Incorporating patient-reported outcomes, such as quality of life and symptom burden, can help inform treatment decisions and improve patient-centered care.
• Immunotherapy: Immunotherapy, which harnesses the power of the immune system to target cancer cells, is a promising area of research that has already shown success in treating certain cancers. Further research is needed to identify biomarkers and develop personalised immunotherapies.
• Rare cancers: Precision medicine has the potential to benefit patients with rare cancers, who often have limited treatment options. Research into rare cancers and the development of targeted therapies is a growing area of focus.
• Global collaboration: Collaboration among researchers, clinicians, and healthcare systems across the globe can accelerate the development and implementation of precision medicine and improve access to these technologies for patients worldwide.

CONCLUSION

Precision medicine in cancer biology is a rapidly evolving field with the potential to transform cancer care and improve patient outcomes. Precision medicine can target specific genetic mutations and biomarkers by using genetic and molecular profiling to personalize treatment, leading to more effective and less toxic therapies. Although there are challenges and limitations to implementing precision medicine, such as cost, complexity, and privacy concerns, ongoing research and development in multi-omics approaches, artificial intelligence, and immunotherapy hold promise for overcoming these challenges and expanding access to these technologies and treatments. With continued global collaboration and a patient-centered approach, precision medicine has the potential to revolutionize cancer care and improve the lives of millions of people worldwide.

REFERENCES

1. National Cancer Institute. (2022). Precision Medicine in Cancer Treatment. Retrieved from https://www.cancer.gov/about-cancer/treatment/types/precision-medicine
2. Garraway, L. A. (2018). Genomics-driven oncology: a framework for an emerging paradigm. Journal of Clinical Oncology, 36(14), 1416–1421. https://doi.org/10.1200/JCO.2017.75.6760
3. Roychowdhury, S. (2016). I Am a Cancer Patient—Will I Benefit from the Genomic Revolution? JAMA Oncology, 2(1), 12–14. https://doi.org/10.1001/jamaoncol.2015.3546
4. Gagan, J., & Van Allen, E. M. (2015). Next-generation sequencing to guide cancer therapy. Genome Medicine, 7(1), 1–13. https://doi.org/10.1186/s13073-015-0162-2
5. Kalia, M. (2015). Biomarkers for personalised oncology: recent advances and future challenges. Metabolism, 64(3), S16–S21. https://doi.org/10.1016/j.metabol.2014.10.019
6. Lambin, P., Leijenaar, R. T. H., Deist, T. M., Peerlings, J., de Jong, E. E. C., van Timmeren, J., … Oberije, C. (2017). Radiomics: the bridge between medical imaging and personalised medicine. Nature Reviews Clinical Oncology, 14(12), 749–762. https://doi.org/10.1038/nrclinonc.2017.141
7. Tsimberidou, A. M., & Kurzrock, R. (2014). Precision Medicine: Lessons Learned from the SHIVA Trial. The Lancet Oncology, 15(3), e117–e124. https://doi.org/10.1016/S1470-2045(13)70569-7
8. Meric-Bernstam, F., & Johnson, A. M. (2013). Precision Medicine: Application of the Molecular Profile in Clinical Oncology. Clinical Pharmacology and Therapeutics, 93(4), 311–318. https://doi.org/10.1038/clpt.2012.227
9. Laskin, J., Jones, S., Aparicio, S., & Chia, S. (2015). Personalised medicine and oncology practice guidelines: a case study of contemporary biomarkers in colorectal cancer. Journal of Personalized Medicine, 5(2), 79–91. https://doi.org/10.3390/jpm5020079
10. Schwaederle, M., Zhao, M., Lee, J. J., Lazar, V., Leyland-Jones, B., & Schilsky, R. L. (2015). Association of Biomarker-Based Treatment Strategies With Response Rates and Progression-Free Survival in Refractory Malignant Neoplasms: A Meta-analysis. JAMA Oncology, 1(4), 460–467. https://doi.org/10.1001/jamaoncol.2015.1313
11. Salami, A., & Detsky, A. S. (2017). Precision medicine: the opportunities and challenges of personalised cancer therapy. CA: A Cancer Journal for Clinicians, 67(6), 460-462.
12. Van Allen, E. M., & Garraway, L. A. (2019). Emerging strategies for the application of clinical genomics to cancer management. Genome Medicine, 11(1), 1–14. https://doi.org/10.1186/s13073-019-0631-y
13. Kim, C., & Prasad, V. (2019). Cancer immunotherapy: dead or alive? The Lancet Oncology, 20(12), 1575–1577. https://doi.org/10.1016/S1470-2045(19)30679-7
14. Zhang, Y., & Liu, S. (2020). Precision medicine: personalising treatment for pancreatic cancer. Discovery Medicine, 29(160), 97–105.
15. D’Angelo, S. P., & Pratilas, C. A. (2016). A Decade of Advances in Precision Oncology. Nature Reviews Clinical Oncology, 13(11), 735–746. https://doi.org/10.1038/nrclinonc.2016.139
16. Pagnan, G., Di Bello, C., Garofoli, M., & Bronte, G. (2021). Artificial Intelligence and Deep Learning in Precision Medicine: A Review on Current Concepts, Applications, and Challenges. Frontiers in Oncology, 11, 639119. https://doi.org/10.3389/fonc.2021.639119
17. U.S. Food and Drug Administration. (2022). Precision Medicine in Oncology. Retrieved from https://www.fda.gov/about-fda/oncology-center-excellence/precision-medicine-oncology.
18. Beauchamp, T. L., & Childress, J. F. (2019). Principles of Biomedical Ethics. Oxford University Press.
19. Rothstein, M. A. (2019). Genetic Discrimination: An Overview of the Legal Landscape. Annual Review of Genomics and Human Genetics, 20, 161-180.
20. Knoppers, B. M., Harris, J. R., Budin-Ljøsne, I., & Dove, E. S. (2014). A human rights approach to an international code of conduct for genomic and clinical data sharing. Human Genetics, 133(7), 895-903.
21. Clayton, E. W. (2016). Ethical, legal, and social implications of genomic medicine. The New England Journal of Medicine, 375(8), 712-714.
22. Terry, S. F., & Terry, P. F. (2019). Power to the people: Participant ownership of clinical trial data. Science Translational Medicine, 11(498), eaaw0126.
23. McGuire, A. L., Fisher, R., & Cusenza, P. (2020). Confidentiality, privacy, and security of genetic and genomic test information in electronic health records: Points to consider. Genetics in Medicine, 22(3), 15-20.
24. Pearson, S. D., & Raeke, L. H. (2000). Patients’ trust in physicians: Many theories, few measures, and little data. Journal of General Internal Medicine, 15(7), 509-513.
25. Prainsack, B. (2017). Personalized medicine: Empowered patients in the 21st century? Genome Medicine, 9(1), 1-8. Prainsack’s work explores personalized medicine and its impact on patient empowerment, a crucial aspect of precision medicine’s ethical landscape.
26. Caulfield, T., & Murdoch, B. (2017). Genes, cells, and biobanks: There is still a consent problem. PLoS Biology, 15(7), e2002654.
27. Sarangi, S., & Clarke, A. (2002). Zones of expertise and the management of uncertainty in genetic risk communication. Discourse & Society, 13(2), 199-218.