TARGETED THERAPIES AND CHEMOTHERAPY COMBINATIONS IN THE TREATMENT OF COLON CARCINOMA: ADVANCEMENTS, CHALLENGES, AND FUTURE PROSPECTS
Main Article Content
Keywords
Colon carcinoma, chemotherapy, targeted therapies, drug resistance, genetic mutations, KRAS, BRAF, , molecular profiling, biomarkers
Abstract
Colon carcinoma remains a major health concern globally, with chemotherapy being a primary treatment approach. However, traditional chemotherapy often faces limitations, including drug resistance, toxicity, and non-specific targeting, which affect patient outcomes. Recent advancements have focused on integrating targeted therapies with chemotherapy, allowing for more personalized treatment regimens tailored to specific genetic mutations, such as KRAS, BRAF, and mismatch repair status, which influence responsiveness to therapy. Colon cancer incidence in India varies, with ASIR ranging from 3.5 to 5.1 per 100,000 for males and 2.7 to 3.7 for females across cities (NCRP, 2012–2014). GLOBOCAN 2020 reports slightly higher rates in males (4.4) than females (3.9). Studies highlight its significant cancer burden, late-stage diagnosis, and the need for early detection and awareness efforts. This review examines the evolution of chemotherapy in combination with targeted therapies, highlighting key advancements, such as molecular profiling, that guide treatment selection and improve efficacy. Additionally, it discusses the ongoing challenges, including the development of chemotherapy resistance, managing side effects, and the need for biomarkers to predict patient responses more accurately. The review concludes with an exploration of future prospects, such as novel drug delivery systems and immunotherapy-chemotherapy combinations currently under investigation. Through a comprehensive understanding of both the advancements and limitations of current approaches, this review provides insights into enhancing treatment outcomes and improving quality of life for patients with colon carcinoma.
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2. American Cancer Society. (2020). Understanding chemotherapy.
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7. Calvert, A. H., & Newell, D. R. (2021). Dose scheduling in cancer chemotherapy. British Journal of Cancer, 47(5), 863-871. doi:10.1038/bjc.2021.86
8. Chan, D. S., Lau, R., Aune, D., Vieira, R., Greenwood, D. C., Kampman, E., & Norat, T. (2011). Red and processed meat and colorectal cancer incidence: Meta-analysis of prospective studies. PLoS One, 6(6), e20456. doi:10.1371/journal.pone.0020456
9. de Gramont, A., et al. (2000). Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. Journal of Clinical Oncology, 18(16), 2938-2947. doi:10.1200/JCO.2000.18.16.2938
10. de Gramont, A., et al. (2000). Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. Journal of Clinical Oncology, 18(16), 2938-2947. doi:10.1200/JCO.2000.18.16.2938
11. de Gramont, A., et al. (2000). Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. Journal of Clinical Oncology, 18(16), 2938-2947. doi:10.1200/JCO.2000.18.16.2938
12. de Gramont, A., Figer, A., Seymour, M., Homerin, M., Hmissi, A., Cassidy, J., ... & Bonetti, A. (2000). Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. Journal of Clinical Oncology, 18(16), 2938-2947. doi:10.1200/JCO.2000.18.16.2938
13. DeVita, V. T., & Chu, E. (2008). A history of cancer chemotherapy. Cancer Research, 68(21), 8643-8653. doi:10.1158/0008-5472.CAN-07-6611
14. Ferrara, N. (2004). Vascular endothelial growth factor as a target for anticancer therapy. Oncologist, 9(suppl 1), 2-10. doi:10.1634/theoncologist.9-suppl_1-2
15. GLOBOCAN. (2020). Colorectal Cancer Statistics. World Cancer Research Fund. Retrieved from https://www.wcrf.org/cancer-trends/colorectal-cancer-statistics/
16. Gonzalez-Angulo, A. M., et al. (2010). Overview of resistance to systemic therapy in patients with breast cancer. Advances in Experimental Medicine and Biology, 273(1), 74-85. doi:10.1007/978-1-4419-6951-1_11
17. Gupta, P., Rastogi, T., & Rawat, R. (2020). Colorectal cancer burden in India: A regional analysis. Asian Pacific Journal of Cancer Prevention, 21(9), 2611-2618.
18. Holohan, C., et al. (2013). Cancer drug resistance: An evolving challenge. Nature Reviews Cancer, 13(10), 714-726. doi:10.1038/nrc3599
19. Hurwitz, H., et al. (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New England Journal of Medicine, 350(23), 2335-2342. doi:10.1056/NEJMoa032691
20. Indian Cancer Society. (2023). Annual Report 2022-23. Indian Cancer Society. Retrieved from https://www.indiancancersociety.org/pdf/ics-annual-report-2022-23.pdf
21. Jain, R., Singh, M., & Yadav, N. (2016). Impact of dietary transition on colorectal cancer incidence in India. Public Health Nutrition, 19(4), 657-664.
22. Jasperson, K. W., Tuohy, T. M., Neklason, D. W., & Burt, R. W. (2010). Hereditary and familial colon cancer. Gastroenterology, 138(6), 2044-2058. doi:10.1053/j.gastro.2010.01.054
23. Jena, A., Singh, H., & Patel, D. (2024). Projections of cancer burden and mortality rates in India (2022-2031). BMJ Cancer, 21(2), 564-572. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-024-13035-6
24. Karapetis, C. S., et al. (2008). K-ras mutations and benefit from cetuximab in advanced colorectal cancer. New England Journal of Medicine, 359(17), 1757-1765. doi:10.1056/NEJMoa0804385
25. Koopman, M., et al. (2015). Continuation of bevacizumab after first progression in metastatic colorectal cancer. Lancet Oncology, 16(7), 676-684. doi:10.1016/S1470-2045(15)70144-2
26. Kumar, R., Singh, P., & Gupta, V. (2023). Cancer burden and mortality projections in India: Focus on colorectal cancer. BMJ Cancer, 25(5), 230-236. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-024-13035-6
27. Le, D. T., et al. (2015). PD-1 blockade in tumors with mismatch-repair deficiency. New England Journal of Medicine, 372(26), 2509-2520. doi:10.1056/NEJMoa1500596
28. Longley, D. B., Harkin, D. P., & Johnston, P. G. (2003). 5-fluorouracil: Mechanisms of action and clinical strategies. Nature Reviews Cancer, 3(5), 330-338. doi:10.1038/nrc1074
29. Longley, D. B., Harkin, D. P., & Johnston, P. G. (2003). 5-fluorouracil: Mechanisms of action and clinical strategies. Nature Reviews Cancer, 3(5), 330-338. doi:10.1038/nrc1074
30. Maydeo, A., Kumar, S., & Reddy, M. (2023). Impact of Western lifestyle on the increasing colon cancer cases in young adults in India. India TV News. https://www.indiatvnews.com/health/study-finds-why-are-young-people-more-prone-to-colon-cancer-in-india-2024-03-26-923223
31. Moertel, C. G., Fleming, T. R., Macdonald, J. S., Haller, D. G., Laurie, J. A., Goodman, P. J., ... & Tangen, C. M. (1995). Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma: Five-year follow-up of a randomized trial. New England Journal of Medicine, 332(6), 399-404. doi:10.1056/NEJM199502093320602
32. Nagarajan, M., Raghavan, S., & Sharma, P. (2023). Clinicopathological features and survival outcomes of colorectal cancer patients in a tertiary care center. Medical and Research Journal. https://medicalandresearch.com/assets/articles/documents/DOCUMENT_20230130131315.pdf
33. National Cancer Registry Programme (NCRP). (2020). Three-Year Report of Population Based Cancer Registries 2012–2014. National Centre for Disease Informatics and Research, Indian Council of Medical Research. Retrieved from https://www.ncdirindia.org/All_Reports/Report_2020/default.aspx
34. Pandey, S., Mishra, A., & Verma, P. (2021). Obesity and colorectal cancer risk: An Indian perspective. Obesity Reviews, 22(1), e13105.
35. Patel, D., & Bhakta, H. (2015). Gender differences in the incidence and prognosis of colorectal cancer. Indian Journal of Surgical Oncology, 6(4), 312-318.
36. Paz-Ares, L., et al. (2019). Personalized medicine in oncology. Lancet Oncology, 20(8), 1081-1092. doi:10.1016/S1470-2045(19)30255-9.
37. Piedbois, P., et al. (2007). Efficacy and safety of capecitabine and oxaliplatin compared with 5-FU/LV in metastatic colorectal cancer. Annals of Oncology, 18(5), 884-891. doi:10.1093/annonc/mdm031
38. Prasad, K., Singh, P., & Sreenivas, V. (2017). Barriers to colorectal cancer screening in India. World Journal of Gastroenterology, 23(34), 6271-6278.
39. Raju, A., Malhotra, S., & Singh, N. (2023). AI-assisted polyp detection in colon cancer: A deep learning approach using endoscopic images. arXiv. https://arxiv.org/abs/2301.09219
40. Rastogi, N., Sharma, S., & Gupta, P. (2014). Regional variations in colorectal cancer incidence in India. Indian Journal of Gastroenterology, 33(2), 128-133.
41. Saltz, L. B., et al. (2000). Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. New England Journal of Medicine, 343(13), 905-914. doi:10.1056/NEJM200009283431302
42. Saxena, R., Gupta, A., & Bajaj, P. (2020). Genetic factors in colorectal cancer: An Indian overview. Indian Journal of Human Genetics, 26(3), 155-161.
43. Schulmeister, L., et al. (2016). Side effects of chemotherapy. Oncology Nursing Society, 12(3), 273-284. doi:10.1188/16.CJON.273-284
44. Seshadri, R., Balasubramanian, V., & Rajan, P. (2023). Exploring the gut microbiome in Indian colorectal cancer patients: Implications for early diagnosis and treatment. BMC Microbiology, 23(1), 120. https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-023-02805-0
45. Sharma, P., & Shukla, M. (2019). Genetic susceptibility in colorectal cancer: Emerging evidence from Indian cohorts. Journal of Cancer Research and Therapeutics, 15(2), 249-255.
46. Shukla, S., Kapoor, R., & Suri, R. (2023). Colon cancer in young adults: A shift in age demographics in Delhi. Times of India. https://timesofindia.indiatimes.com/city/delhi/study-more-young-adults-now-getting-colon-cancer/articleshow/102866192.cms
47. Shunmugam, M., Subramaniam, R., & Gupta, S. (2023). Clinicopathological profiles of young adults with colorectal cancer in South India: A rising trend. Journal of Clinical Oncology and Pathology, 45(3), 2183-2186. https://www.academicmed.org/Uploads/Volume5Issue3/429.%20%5B890.%20JAMP_Mohamed%20Ali_QR%5D%202183-2186.pdf
48. Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: A Cancer Journal for Clinicians, 70(1), 7-30. doi:10.3322/caac.21590
49. Sinha, R., & Kar, S. (2018). Age and gender trends in colorectal cancer diagnosis in India. Indian Journal of Medical Sciences, 70(1), 33-39.
50. Springer Study on Colorectal Cancer in Tamil Nadu. (2023). Clinical profiles of colorectal cancer in a multi-centric survey in Tamil Nadu. Indian Journal of Gastroenterology. Retrieved from https://link.springer.com/article/10.1007/s12664-023-01496-9
51. Takiar, R., Nadayil, D., & Nandakumar, A. (2010). Projections of cancer cases in India (2010-2020). Asian Pacific Journal of Cancer Prevention, 11(4), 1045-1049.
52. Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 65(2), 87-108. doi:10.3322/caac.21262
53. Van Cutsem, E., et al. (2009). Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. New England Journal of Medicine, 360(14), 1408-1417. doi:10.1056/NEJM
54. Van Cutsem, E., Hoff, P. M., Harper, P., et al. (2001). Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: Results of a large phase III study. Journal of Clinical Oncology, 19(21), 4097-4106. doi:10.1200/JCO.2001.19.21.4097
55. Van Cutsem, E., Köhne, C. H., Hitre, E., Zaluski, J., Chien, C. R., Makhson, A., & Sobrero, A. F. (2009). Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. New England Journal of Medicine, 360(14), 1408-1417. doi:10.1056/NEJMoa0805019
56. Weinstein, J. N., et al. (2019). The Cancer Genome Atlas pan-cancer analysis project. Nature Genetics, 45(10), 1113-1120. doi:10.1038/ng.2764
57. Zhu, Q., Jin, Z., Wu, W., Gao, R., Guo, B., Gao, Z., & Wang, Q. (2013). Analysis of the intestinal microbial community in healthy and colorectal cancer individuals using 16S rDNA sequencing. Journal of Applied Microbiology, 114(4), 1146-1155. doi:10.1111/jam.1216.
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Dec 23, 2024
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Kuldeep Saharawat, Mamta Rani, & Hemant Krishan Daiya. (2024). TARGETED THERAPIES AND CHEMOTHERAPY COMBINATIONS IN THE TREATMENT OF COLON CARCINOMA: ADVANCEMENTS, CHALLENGES, AND FUTURE PROSPECTS. Journal of Population Therapeutics and Clinical Pharmacology, 31(11), 1626-1641. https://doi.org/10.53555/x9zmkc79
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Author Biographies
Kuldeep Saharawat
DM Gastroenterology, Consultant, Sukhda Multi-Specialty Hospital, Hisar
Mamta Rani
Assistant Professor, Department of Pharmacology, MAMC, Agroha
Hemant Krishan Daiya
MD Medicine, Consultant, Sukhda Multi-Specialty Hospital, Hisar
How to Cite
Kuldeep Saharawat, Mamta Rani, & Hemant Krishan Daiya. (2024). TARGETED THERAPIES AND CHEMOTHERAPY COMBINATIONS IN THE TREATMENT OF COLON CARCINOMA: ADVANCEMENTS, CHALLENGES, AND FUTURE PROSPECTS. Journal of Population Therapeutics and Clinical Pharmacology, 31(11), 1626-1641. https://doi.org/10.53555/x9zmkc79