Colonoscopy, Biomarkers, and Targeted Therapy in Colorectal Cancer
Keywords:
Colonoscopy, colorectal cancer, biomarkers, cancer stem cells, targeted therapyAbstract
This review highlights the most versatile diagnostic test of colonoscopy for CRC. It remains the gold standard diagnostic tools for CRC, and to prevent CRC by screening and removing the polyp or premalignant lesions. This work also provides the most promising biomarkers, which highlights the application of the novel biomarkers in conjunction with clinical and pathologic features have allowed for more individualized approaches and targeted therapy to patients with CRC.CRC is the third most common cancer diagnosed, and the second leading cause of cancer-related deaths worldwide. With a population totaling 273,523,621 people, Indonesia has an estimated of 396,914 new cases of all cancers and 234,511 cancer-related deaths. Among those cancer cases, an estimated of 34,189 new CRC cases and 17,786 CRC deaths occurred in 2020. Most of CRC cases were located in the rectum compared to those in the distal colon or proximal colon. Clinical signs, symptoms and therapeutic approaches vary, depending on the stage and the location of CRC. Those cancer locations are different in terms of their associated molecular alterations.Biomarker tests of tumor tissue from colonoscopy biopsy can help doctors to select a specific CRC treatment, and the tests can be used to determine prognostic value, predictive factors and the targeted therapy. Targeted therapies are recommended for advanced or mCRC patients with KRAS/NRAS/BRAF mutated or wild-type tumors, HER2-amplified tumors, and NTRK gene fusion-positive, while immunotherapy is only offered for tumor with MSI-High (dMMR) status. The biomarkers and targeting approaches against colorectal CSCs are being developed and will be quite challenging.References
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 04 February 2021. Cancer J for Clin 2021;71(3):209-49. Accessed August 14, 2021.
Globocan 2020. Indonesia-Global Cancer Observatory. Available on online: https://gco.iarc.fr/to day/factsheets/populations/360-indonesia-fact-sheets.
Effendi-YS R. Cancer stem cells and molecular biology test in colorectal cancer: therapeutic implications. Acta Med Indones-Indones J Intern Med. 2017;49(4): 351-9.
Effendi-YS R, Zain LH, Siregar GA, et al. Adenomatous polyposis coli, mismatch repair, and microsatellite instability in colorectal cancer based on locations. Acta Med Indones. 2013;45(4):275-83. PubMed. https://www.ncbi.nlm.nih.gov/pubmed/24448331#
Shaukat A, Kahi CJ, Burke CA, Rabeneck L, Sauer BG, and Reg DA. ACG clinical guidelines: colorectal cancer screening 2021. Am J Gastroenterol. 2021;116:458-79. https://doi.org/10.14309/ajg.0000000000001122. Accessed August 14,2021.
Crockett SD, Nagtegaal I. Terminology, molecular features, epidemiology, and management of serrated colorectal neoplasia. Gastroenterology 2019;157(4):949-966.e4. doi: 10.1053/j.gastro.2019.06.041. Epub 2019 Jul 16. PMID: 31323292.
Effendi-YS R, Rey I. Molecular diagnostics in colorectal cancer. The Indonesia J of Gastroenterol Hepatol and Dig Endoscopy. 2015;16(1):26-33.
Patsalias A, Kozovska Z. Personalized medicine: stem cells in colorectal cancer treatment. Elsevier. Biomedicine & Pharmacotherapy 141(2021) 111821. https://doi.org/10.1016/ j.biopha.2021.11.111821
Effendi-YSR, Rey I. Cancer stem cells and signaling pathways in colorectal cancer. The Indonesian J of Gastroenterol Hepatol and Dig Endoscopy. 2018;19(1): 37-40.
Herszenyl L. The difficult colorectal polyps and adenomas: practical aspects. Dig Dis. 2019;37(5): 394-9. doi: 10.1159/000495694. Epub 2018 Dec 12. PMID: 30540996.
Lim XC, Nistala KRY, Ng CH, et al. Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal polyps: a meta-analysis and meta-regression with single arm analysis. World J Gastroenterol. 2021;27(25):3925-39.
Holtedahl K, Borgquist L, Donker GA, et al. Symptoms and signs of colorectal cancer, with differences between proximal and distal colon cancer: a prospective cohort study of diagnostic accuracy in primary care. BMC Fam Pract. 2021;22(1): 148. doi: 10.1186/s12875-021-01452-6. PMID: 34238248; PMCID: PMC8268573.
Riihimaki M, Hemminki A, Sundquist J, Hemminki K. Patterns of metastasis in colon and rectal cancer. Scientific Reports 2016;6(1):29765. doi: ID.10381/srep29765.
Yang J, Du XL, Li ST, et al. Characteristics of differently located colorectal cancers support proximal and distal classification: a population-based study of 57,847 patients. PLoS One. 2016;11(12):e0167540. doi: 10.1371/journal.pone.0167540.
Mayer RJ. Lower gastrointestinal cancers. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. Harrison’s gastroenterology and hepatology. 3rd ed. New York: McGraw-Hill; 2017. p. 549-58.
Zamarin D, Saltz L. Colon cancer, rectal cancer. In Drilon AE, Postow MA, Krug LM, eds. Pocket oncol. Philadelpia: Wolters Kluwer. Lippincott Williams & Wilkins; 2014. p. 156-9.
Koncina E, Haan S, Rauh S, Letellier E. Prognostic and predictive molecular biomarkers for colorectal cancer: updates and challenges. Cancer. 2020;12(2):319. doi:10.3390/cancers12020319.
Lieu CH, Corcoran RB, Overman MJ. Integrating biomarkers and targeted therapy into colorectal cancer management. Ascopubs.org.2019 Asco Educational Book. Doi https://.doi.org/10.1200/EDBK.240839.
Grady WM, Pritchard CC. Molecular alterations and biomarkers in colorectal cancer. Toxicologic Pathol. 2014;42:124-39. Doi: 10.1177/0192623313505155.
Huth L, Jakel J, Dahl E. Molecular diagnostic applications in colorectal cancer. Microarrays. 2014;3:168-79. doi:10.3390/microarrays3030168
Ronnekleiv-Kelly SM, Burkhart RA, Pawlik TM. Molecular markers of prognosis and therapeutic targets in metastatic colorectal cancer. Surg Oncol. 2016;25(3):190-9. doi: 10.1016/j.suronc.2016.05.018. Epub 2016 May 20. PMID: 27566022; PMCID: PMC5152574
Battaglin F, Naseem M, Salem ME. Microsatellite instability in colorectal cancer. Overview of its clinical significance and novel perspectives. Clin Adv Hematol Oncol. 2018;16(11):735-45.
Malki A, ElRuz RA, Gupta I, Allouch A, Vranic S, Al Moustafa AE. Molecular mechanism of colon cancer progression and metastasis: Recent insight and advancements. Int J Mol Sci. 2021;22:130. http://dx.doi.org/10.3390/ijms22010130.
Coppede F, Lopomo A, Spisni R, Migliore L. Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer. World J Gastroenterol 2014:20(4):943-56.
Pang S-W, Awi NJ, Armon S, et al. Current update of laboratory molecular diagnostics advancement in management of colorectal cancer (CRC). Diagnostics. 2020;10:9. https://doi.org/10.3390/ diagnos tics10010009
To KK, Tong CW, Wu M, Cho WC. Micrornas in the prognosis and therapy of colorectal cancer: from bench to bedside. World J Gastroenterol. 2018;24(27):2949-73. doi: 10.3748/wjg.v24.i27.2949. PMID: 30038463; PMCID: PMC6054943
Strubberg, Ashlee M, Madison, Blair B. MicroRNAs in the etiology of colorectal cancer: Pthways and clinical implications. Disease Models & Mechanisms. 2017;10:3.197.214. https://digitalcommons.wustl.edu/open_access_puba/5644
Prasetyanti PR, Medema JP. Intra-tumor heterogeneity from a cancer stem cell perspective. Molecular Cancer. 2017;16:41. Doc.10.1186/s 12943-017-0600-4.
Song L, Li Y, He B, Gong Y. Development of small molecules targeting the wnt signaling pathway in cancer stem cell for the treatment of colorectal cancer. Clin Colorectal Cancer. 2015;14:133-45.
Parizadeh SM, Jafarzadeh-Esfehani R, Hassanian SM, et al. Targeting cancer stem cells as therapeutic approach in the treatment of colorectal cancer. Int J Biochem Cell Biol. 2019;110:75-83. Doi: 10.1016/J.biocel. 2019.02.010.
Effendi YSR, Imelda Rey, Khadafi M. Neoplasma usus besar (colorectal neoplasm). In: Effendi YSR ed. Penatalaksanaan klinis kelainan gastrointestinal (clinical management of gastro intestinal disorders). Jakarta: EGC; 2019. p. 263-76.
Hasler WL, Owyang C. Approach to the patient with gastrointestinal disease. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo JL, eds. Harrison’s gastroenterology and hepatology. 3rd ed. McGraw-Hill Educ,co.Inc; 2017. p. 80-8.
Nakayama G, Tanaka C, Kodera Y. Current options for the diagnosis, staging and therapeutic management of colorectal cancer. Gastrointest Tumors. 2014;1:25-32. https:/doi.org/ 10.1159/000354995.
Effendi-YSR. Economic burden of colorectal cancer: prevention vs treatment. In: Simadibrata M, Makmun D, Abdullah M, Syam AF, eds. Proceeding book. Indonesian digestive disease week. Jakarta: Interna Publishing; 2016. p. 50-8.
Yuan Y, Wang X, Chen G, et al. Updates in version 2019 of csco guidelines for colorectal cancer from version 2018. Clin J Cancer Res. 2019;31(3):423-5.
Seal BS, Sullivan SD, Ramsey S, et al. Medical costs associated with use of systemic therapy in adults with colorectal cancer. J Manag Care Pharm. 2013;19(6):461-7.
Han L, Shi S, Gong T, Zhang Z, Sun X. Cancer stem cells: therapeutic implications and perspective in cancer therapy. Acta Phar Sinica B. 2013;3(2): 65-75.
Song L, Li Y. The role of stem cell dna methylation in colorectal carcinogenesis. Stem Cell Rev Rep. doi10.1007/s12015-016-9672-6. Springer. Published online: 11 July 2016.
Ma YS, Li W, Liu Y, Shi Y, Lin QL, Fu D. Targeting colorectal cancer stem cells as an effective treatment for colorectal cancer. Technology in Cancer Research & Treatment. 2020;19:1-9. DOI: 10.1177/1533033819892261 journals.sagepub. com/ home/tct. Accessed August 14 2021.
Zhou Y, Xia L, Wang H, et al. Cancer stem cells in progression of colorectal cancer. Oncotarget. 2018;9(70):33403-15. www.oncotarget.com
Yang L, Shi P, Zhao G, et al. Targeting cancer stem cell pathways for cancer therapy. Signal Transduction and Targeted Therapy. 2020;5:8. https://doi.org/10.1038/s41392-020-0110-5. Accessed Agustus 14, 2021.
Hervieu C, Christou N, Battu S, Mathonnet M. The role of cancer stem cells in colorectal cancer: from the basics to novel clinical trials. Cancers. 2021;13:1092. https://doi.org/ 10.3390/cancers13051092
Zhao Y, Dong Q, Li J, et al. Targeting cancer ctem cells and their niche: perspective for futere therapeutic targets and strategies. Semin. Cancer Biol. 2018;53: 139-55.
Taniguchi H, Moriya C, Igarashi H, et al. Cancer stem cells in human gastrointestinal cancer. Cancer Sci. 2016;107(11):1556-62.
Kim WT, Ryu CJ. Cancer stem cell surface markers on normal stem cells. BMB Rep. 2017;50(6):285-98. doi: 10.5483/bmbrep.2017.50.6.039.
Huyghe N, Baldin P, Van den Eynde M. Immunotherapy with immune checkpoints in colorectal cancer: what is the future beyond deficient mismatch repair tumours? Gastroenterology Report. 2020;8(1):11-24.
Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair defiency. N Engl J Med. 2015;372:2509-20.
Overman MJ, Lonardi S, Wong KYM, et al. Durable clinical benefit with nivolumab plus ipilimumab in dna mismatch repair deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018; 36(8):773-9.
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