Genomic Profiling for Precision Cancer Therapies
Md Shamsuddin Sultan Khan 1*, Fouad Saleh Resq Al-Suede 2, Mohamed Khadeer Ahamed Basheer 2 , Amin Malik Shah Abdul Majid 3
Journal of Precision Biosciences 3(1) 1-12 https://doi.org/10.25163/biosciences.310032
Submitted: 02 January 2024 Revised: 18 February 2021 Published: 20 February 2021
Genetic profiling revolutionizing precision cancer therapies, offering personalized treatments and reshaping oncology's development for enhanced patient outcomes.
Abstract
The transformative power of genetic profiling on the field of precision cancer medicines is examined in this review, which also clarifies the methodological nuances and broad ramifications of incorporating genomic data into clinical oncology. A novel method called “genomic profiling” examines cancer DNA thoroughly to identify particular genetic changes, mutations, and biomarkers that influence tumor activity. Next-generation sequencing (NGS) is a cutting-edge technique for genomic profiling that makes whole-genome sequencing quick and affordable. Thanks to NGS, doctors may now better understand the molecular causes of cancer and develop individualized treatment plans by identifying exact genetic fingerprints. The paper explores the clinical uses of genomic profiling and shows how it can help inform treatment choices by detecting genetic abnormalities that can be targeted, allowing for a deviation from the standard homogeneous therapy paradigms.Genomic profiling-based customized cancer care has far-reaching ramifications. Through the alignment of therapies with the unique genetic composition of each patient’s cancer, medical professionals maximize therapy effectiveness while reducing side effects. Beyond clinical applications, the influence on healthcare systems is discussed, emphasizing the need for worldwide standardization, interdisciplinary collaboration, and the construction of a strong infrastructure in order to fully realize the promise of precision cancer therapy.Finally, genetic profiling becomes clear as a keystone in the development of oncology, changing patient outcomes and therapeutic approaches. In order to bring in a new era of precision cancer care, the paper emphasizes the vital significance of continued research, technology developments, and calculated partnerships in establishing genetic profiling as a fundamental part of regular clinical practice.
Keywords: Genomic Profiling, Precision Cancer Therapies,. Next-Generation Sequencing (NGS), Personalized Medicines
References
Adashek, J. J., Kato, S., Lippman, S. M., & Kurzrock, R. (2020). The paradox of cancer genes in non-malignant conditions: implications for precision medicine. Genome medicine, 12, 1-19.
Allgäuer, M., Budczies, J., Christopoulos, P., Endris, V., Lier, A., Rempel, E., … & Stenzinger, A. (2018). Implementing tumor mutational burden (TMB) analysis in routine diagnostics—a primer for molecular pathologists and clinicians. Translational lung cancer research, 7(6), 703.
Andre, F., Ismaila, N., Henry, N. L., Somerfield, M. R., Bast, R. C., Barlow, W., … & Stearns, V. (2019). Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: ASCO clinical practice guideline update—integration of results from TAILORx. Journal of Clinical Oncology, 37(22), 1956-1964.
André, T., Shiu, K. K., Kim, T. W., Jensen, B. V., Jensen, L. H., Punt, C., … & Diaz Jr, L. A. (2020). Pembrolizumab in microsatellite-instability–high advanced colorectal cancer. New England Journal of Medicine, 383(23), 2207-2218.
Berger, M. F., & Mardis, E. R. (2018). The emerging clinical relevance of genomics in cancer medicine. Nature reviews Clinical oncology, 15(6), 353-365.
Bernstein, B. E., Stamatoyannopoulos, J. A., Costello, J. F., Ren, B., Milosavljevic, A., Meissner, A., … & Thomson, J. A. (2010). The NIH roadmap epigenomics mapping consortium. Nature biotechnology, 28(10), 1045-1048.
Brabetz, S., Leary, S. E., Gröbner, S. N., Nakamoto, M. W., Seker-Cin, H., Girard, E. J., … & Olson, J. M. (2018). A biobank of patient-derived pediatric brain tumor models. Nature medicine, 24(11), 1752-1761.
Brown, N. A., & Elenitoba-Johnson, K. S. (2020). Enabling precision oncology through precision diagnostics. Annual Review of Pathology: Mechanisms of Disease, 15, 97-121.
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., … & McArthur, G. A. (2011). Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine, 364(26), 2507-2516.
Chapuy, B., Stewart, C., Dunford, A. J., Kim, J., Kamburov, A., Redd, R. A., … & Shipp, M. A. (2018). Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nature medicine, 24(5), 679-690.
Christofyllakis, K., Bittenbring, J. T., Thurner, L., Ahlgrimm, M., Stilgenbauer, S., Bewarder, M., & Kaddu-Mulindwa, D. (2022). Cost-effectiveness of precision cancer medicine-current challenges in the use of next generation sequencing for comprehensive tumour genomic profiling and the role of clinical utility frameworks. Molecular and Clinical Oncology, 16(1), 1-4.
Collins, F. S., & Varmus, H. (2015). A new initiative on precision medicine. New England journal of medicine, 372(9), 793-795.
Colomer, R., Miranda, J., Romero-Laorden, N., Hornedo, J., González-Cortijo, L., Mouron, S., … & Quintela-Fandino, M. (2023). Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement. EclinicalMedicine, 60.
Colomer, R., Mondejar, R., Romero-Laorden, N., Alfranca, A., Sanchez-Madrid, F., & Quintela-Fandino, M. (2020). When should we order a next generation sequencing test in a patient with cancer?. EclinicalMedicine, 25.
Conway, J. R., Kofman, E., Mo, S. S., Elmarakeby, H., & Van Allen, E. (2018). Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine. Genome medicine, 10(1), 1-18.
Cristescu, R., Mogg, R., Ayers, M., Albright, A., Murphy, E., Yearley, J., … & Kaufman, D. (2018). Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy. Science, 362(6411), eaar3593.
Druker, B. J., Talpaz, M., Resta, D. J., Peng, B., Buchdunger, E., Ford, J. M., … & Sawyers, C. L. (2001). Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. New England Journal of Medicine, 344(14), 1031-1037.
Dugger, S. A., Platt, A., & Goldstein, D. B. (2018). Drug development in the era of precision medicine. Nature reviews Drug discovery, 17(3), 183-196.
Gandara, D. R., Paul, S. M., Kowanetz, M., Schleifman, E., Zou, W., Li, Y., … & Shames, D. S. (2018). Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nature medicine, 24(9), 1441-1448.
Gardner, B., Doose, M., Sanchez, J. I., Freedman, A. N., & de Moor, J. S. (2021). Distribution of genomic testing resources by oncology practice and rurality: a nationally representative study. JCO Precision Oncology, 5, 1060-1068.
Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S. C., Gonzalez, S., Rosebrock, D., … & Van Loo, P. (2020). The evolutionary history of 2,658 cancers. Nature, 578(7793), 122-128.
Guinney, J., Dienstmann, R., Wang, X., De Reynies, A., Schlicker, A., Soneson, C., … & Tejpar, S. (2015). The consensus molecular subtypes of colorectal cancer. Nature medicine, 21(11), 1350-1356.
Gutierrez, M. E., Price, K. S., Lanman, R. B., Nagy, R. J., Shah, I., Mathura, S., … & Goldberg, S. L. (2019). Genomic profiling for KRAS, NRAS, BRAF, microsatellite instability, and mismatch repair deficiency among patients with metastatic colon cancer. JCO Precision Oncology, 3, 1-9.
Haslam, A., Kim, M. S., & Prasad, V. (2021). Updated estimates of eligibility for and response to genome-targeted oncology drugs among US cancer patients, 2006-2020. Annals of Oncology, 32(7), 926-932.
Hellmann, M. D., Ciuleanu, T. E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … & Paz-Ares, L. (2018). Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. New England Journal of Medicine, 378(22), 2093-2104.
Hinoue, T., Weisenberger, D. J., Lange, C. P., Shen, H., Byun, H. M., Van Den Berg, D., … & Laird, P. W. (2012). Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome research, 22(2), 271-282.
Horak, P., Heining, C., Kreutzfeldt, S., Hutter, B., Mock, A., Hüllein, J., … & Fröhling, S. (2021). Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers. Cancer discovery, 11(11), 2780-2795.
Horak, P., Klink, B., Heining, C., Gröschel, S., Hutter, B., Fröhlich, M., … & Fröhling, S. (2017). Precision oncology based on omics data: the NCT Heidelberg experience. International journal of cancer, 141(5), 877-886.
Horak, P., Leichsenring, J., Goldschmid, H., Kreutzfeldt, S., Kazdal, D., Teleanu, V., … & Stenzinger, A. (2022). Assigning evidence to actionability: An introduction to variant interpretation in precision cancer medicine. Genes, Chromosomes and Cancer, 61(6), 303-313.
Ignatiadis, M., Sledge, G. W., & Jeffrey, S. S. (2021). Liquid biopsy enters the clinic—implementation issues and future challenges. Nature reviews Clinical oncology, 18(5), 297-312.
Kim, H., & Park, K. U. (2023). Clinical Circulating Tumor DNA Testing for Precision Oncology. Cancer Research and Treatment: Official Journal of Korean Cancer Association, 55(2), 351-366.
Klughammer, J., Kiesel, B., Roetzer, T., Fortelny, N., Nemc, A., Nenning, K. H., … & Bock, C. (2018). The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space. Nature medicine, 24(10), 1611-1624.
Lamarca, A., Edeline, J., & Goyal, L. (2022). How I treat biliary tract cancer. ESMO open, 7(1), 100378.
Letai, A., Bhola, P., & Welm, A. L. (2022). Functional precision oncology: testing tumors with drugs to identify vulnerabilities and novel combinations. Cancer Cell, 40(1), 26-35.
Li, K., Luo, H., Huang, L., Luo, H., & Zhu, X. (2020). Microsatellite instability: a review of what the oncologist should know. Cancer cell international, 20, 1-13.
Li, M. M., Datto, M., Duncavage, E. J., Kulkarni, S., Lindeman, N. I., Roy, S., … & Nikiforova, M. N. (2017). Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. The Journal of molecular diagnostics, 19(1), 4-23.
Looney, A. M., Nawaz, K., & Webster, R. M. (2020). Tumour-agnostic therapies. Nature Reviews Drug Discovery, 19(6), 383-385.
Malone, E. R., Oliva, M., Sabatini, P. J. B., Stockley, T. L., & Siu, L. L. (2020). Molecular profiling for precision cancer therapies. Genome Med 12: 8.
Massard, C., Michiels, S., Ferté, C., Le Deley, M. C., Lacroix, L., Hollebecque, A., … & Soria, J. C. (2017). High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer discovery, 7(6), 586-595.
Mateo, J., Steuten, L., Aftimos, P., André, F., Davies, M., Garralda, E., … & Voest, E. (2022). Delivering precision oncology to patients with cancer. Nature Medicine, 28(4), 658-665.
Mosele, F., Remon, J., Mateo, J., Westphalen, C. B., Barlesi, F., Lolkema, M. P., … & André, F. (2020). Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Annals of Oncology, 31(11), 1491-1505.
Nebbioso, A., Tambaro, F. P., Dell’Aversana, C., & Altucci, L. (2018). Cancer epigenetics: moving forward. PloS genetics, 14(6), e1007362.
Nielsen, T., Wallden, B., Schaper, C., Ferree, S., Liu, S., Gao, D., … & Storhoff, J. (2014). Analytical validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens. BMC cancer, 14, 1-14.
Parikh, A. R., Leshchiner, I., Elagina, L., Goyal, L., Levovitz, C., Siravegna, G., … & Corcoran, R. B. (2019). Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers. Nature medicine, 25(9), 1415-1421.
Planchard, D., Popat, S. T., Kerr, K., Novello, S., Smit, E. F., Faivre-Finn, C., … & Peters, S. (2018). Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 29, iv192-iv237.
Riedl, J. M., Hasenleithner, S. O., Pregartner, G., Scheipner, L., Posch, F., Groller, K., … & Gerger, A. (2021). Profiling of circulating tumor DNA and tumor tissue for treatment selection in patients with advanced and refractory carcinoma: a prospective, two-stage phase II Individualized Cancer Treatment trial. Therapeutic Advances in Medical Oncology, 13, 1758835920987658.
Robinson, D., Van Allen, E. M., Wu, Y. M., Schultz, N., Lonigro, R. J., Mosquera, J. M., … & Chinnaiyan, A. M. (2015). Integrative clinical genomics of advanced prostate cancer. Cell, 161(5), 1215-1228.
Rodon, J., Soria, J. C., Berger, R., Batist, G., Tsimberidou, A., Bresson, C., … & Kurzrock, R. (2015). Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial. Annals of Oncology, 26(8), 1791-1798.
Rothwell, D. G., Ayub, M., Cook, N., Thistlethwaite, F., Carter, L., Dean, E., … & Krebs, M. G. (2019). Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study. Nature medicine, 25(5), 738-743.
Schumacher, T. N., & Schreiber, R. D. (2015). Neoantigens in cancer immunotherapy. Science, 348(6230), 69-74.
Senft, D., Leiserson, M. D., Ruppin, E., & Ze’ev, A. R. (2017). Precision oncology: the road ahead. Trends in molecular medicine, 23(10), 874-898.
Sorscher, S. (2023). Do All Patients Diagnosed With Cancer Deserve Germline Testing?. Journal of Clinical Oncology, JCO-23.
Stenzinger, A., Allen, J. D., Maas, J., Stewart, M. D., Merino, D. M., Wempe, M. M., & Dietel, M. (2019). Tumor mutational burden standardization initiatives: recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions. Genes, Chromosomes and Cancer, 58(8), 578-588.
Stunnenberg, H. G., Abrignani, S., Adams, D., de Almeida, M., Altucci, L., Amin, V., … & Patel, R. (2016). The International Human Epigenome Consortium: a blueprint for scientific collaboration and discovery. Cell, 167(5), 1145-1149.
Subbiah, V., & Kurzrock, R. (2018). Challenging standard-of-care paradigms in the precision oncology era. Trends in cancer, 4(2), 101-109.
Subbiah, V., & Kurzrock, R. (2023). Universal germline and tumor genomic testing needed to win the war against cancer: Genomics is the diagnosis. Journal of Clinical Oncology, 41(17), 3100-3103.
Tsimberidou, A. M., Fountzilas, E., Nikanjam, M., & Kurzrock, R. (2020). Review of precision cancer medicine: Evolution of the treatment paradigm. Cancer treatment reviews, 86, 102019.
Tutt, A., Tovey, H., Cheang, M. C. U., Kernaghan, S., Kilburn, L., Gazinska, P., … & Bliss, J. M. (2018). Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nature medicine, 24(5), 628-637
Von Hoff, D. D., Stephenson Jr, J. J., Rosen, P., Loesch, D. M., Borad, M. J., Anthony, S., … & Penny, R. (2010). Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol, 28(33), 4877-4883.
Waarts, M. R., Stonestrom, A. J., Park, Y. C., & Levine, R. L. (2022). Targeting mutations in cancer. The Journal of clinical investigation, 132(8).
Weinstein, J. N., Collisson, E. A., Mills, G. B., Shaw, K. R., Ozenberger, B. A., Ellrott, K., … & Stuart, J. M. (2013). The cancer genome atlas pan-cancer analysis project. Nature genetics, 45(10), 1113-1120
Yarchoan, M., Hopkins, A., & Jaffee, E. M. (2017). Tumor mutational burden and response rate to PD-1 inhibition. New England Journal of Medicine, 377(25), 2500-2501.
Yoshimi, A., Lin, K. T., Wiseman, D. H., Rahman, M. A., Pastore, A., Wang, B., … & Abdel-Wahab, O. (2019). Coordinated alterations in RNA splicing and epigenetic regulation drive leukaemogenesis. Nature, 574(7777), 273-277.
Chimento, A., Luca, A. De, Avena, P., Amicis, F. De, Casaburi, I., & Sirianni, R. (2022). Estrogen Receptors-Mediated Apoptosis in HormoneDependent Cancers.
Choi JH, Choi KC, Auersperg N, Leung PC. (2004). Overexpression of follicle-stimulating hormone receptor activates oncogenic pathways in preneoplastic ovarian surface epithelial cells. J Clin Endocrinol Metab;89:5508–5516.
View Dimensions
View Altmetric
Save
Citation
View
Share