Personalized medicine in colorectal cancer
Gastroenterology and Hepatology from Bed to Bench,
Colorectal cancer (CRC) is a heterogeneous disease with various genetic and epigenetic factors leading to difficulties in response to both the therapy and drug resistance. Moreover, even in tumors with similar histopathological characteristics, different responses and molecular features could be observed because of the genetic basis and its interactions with the living environment. Through personalized medicine, we can classify patients into separate groups according to their genetic and epigenetic features and their susceptibility for a specific disease which could help with choosing the best therapeutic approach. In this review, genetic and epigenetic factors that cause heterogeneity in colorectal cancer are evaluated and proper drug administration in both chemotherapy and target therapy are suggested.
Keywords: Colorectal cancer, Personalized medicine, Biomarker, Targeted therapy, Chemotherapy.
(Please cite as: Vaseghi Maghvan P, Jeibouei SH, Akbari ME, Niazi V, Karami F, Rezvani, AR, et al. Personalized medicine in colorectal cancer. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S18-S28).
- Colorectal cancer
- personalized medicine
- targeted therapy
How to Cite
Safaei A, Sobhi S, Rezaei-Tavirani M, Zali MR. Genomic and epigenetic instability in colorectal cancer. Iran J Cancer Prev 2013;6:54-63.
Blanco-Calvo M, Concha Á, Figueroa A, Garrido F, Valladares-Ayerbes M. Colorectal cancer classification and cell heterogeneity: a systems oncology approach. Int J Mol Sci 2015;16:13610-32.
Rezaie-Tavirani M, Fayazfar S, Heydari-Keshel S, Rezaee MB, Zamanian-Azodi M, Rezaei-Tavirani M, et al. Effect of essential oil of Rosa Damascena on human colon cancer cell line SW742. Gastroenterol Hepatol Bed Bench 2013;6:25.
Markowitz SD, Bertagnolli MM. Molecular basis of colorectal cancer. N Engl J Med 2009;361:2449-60.
Lao VV, Grady WM. Epigenetics and colorectal cancer. Nature reviews Gastroenterol Hepatol 2011;8:686.
Herrera M, Islam AB, Herrera A, Martín P, García V, Silva J, et al. Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature. Clin Cancer Res 2013;19:5914-26.
Siena S, Sartore-Bianchi A, Di Nicolantonio F, Balfour J, Bardelli A. Biomarkers predicting clinical outcome of epidermal growth factor receptor–targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 2009;101:1308-24.
Berdiel-Acer M, Sanz-Pamplona R, Calon A, Cuadras D, Berenguer A, Sanjuan X, et al. Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information. Mol Oncol 2014;8:1290-305.
Vermeulen L, Felipe De Sousa EM, Van Der Heijden M, Cameron K, De Jong JH, Borovski T, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 2010;12:468.
Masoodi M, Zali MR, Ehsani-Ardakani MJ, Mohammad-Alizadeh AH, Aiassofi K, Aghazadeh R, et al. Abdominal pain due to lead-contaminated opium: a new source of inorganic lead poisoning in Iran. Arch Iran Med 2006;9:72-5.
Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 2015;5:43-51.
van Zijl F, Krupitza G, Mikulits W. Initial steps of metastasis: cell invasion and endothelial transmigration. Mutati Res 2011;728:23-34.
Gillies RJ, Verduzco D, Gatenby RA. Evolutionary dynamics unifies carcinogenesis and cancer therapy. Nat Rev Cancer 2012;12:487.
Segditsas S, Tomlinson I. Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene 2006;25:7531.
Barzi A, Lenz AM, Labonte MJ, Lenz H-J. Molecular pathways: estrogen pathway in colorectal cancer. Clin Cancer Res 2013;19:5842-8.
Popat S, Hubner R, Houlston R. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 2005;23:609-18.
Deyati A, Bagewadi S, Senger P, Hofmann-Apitius M, Novac N. Systems approach for the selection of micro-RNAs as therapeutic biomarkers of anti-EGFR monoclonal antibody treatment in colorectal cancer. Sci Rep 2015;5:8013.
Matsumura T, Sugimachi K, Iinuma H, Takahashi Y, Kurashige J, Sawada G, et al. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br J Cancer 2015;113:275.
Oldenhuis C, Oosting S, Gietema J, De Vries E. Prognostic versus predictive value of biomarkers in oncology. Eur J Cancer 2008;44:946-53.
Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 2004;287:G7-17.
Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 2009;28:466-74.
Therkildsen C, Bergmann TK, Henrichsen-Schnack T, Ladelund S, Nilbert M. The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: a systematic review and meta-analysis. Acta Oncol 2014;53:852-64.
Nikolouzakis TK, Vassilopoulou L, Fragkiadaki P, Mariolis Sapsakos T, Papadakis GZ, Spandidos DA, et al. Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients. Oncol Rep 2018;39:2455-72.
Bennouna J, Sastre J, Arnold D, Österlund P, Greil R, Van Cutsem E, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013;14:29-37.
Wahid M, Mandal RK, Dar SA, Jawed A, Lohani M, Areeshi MY, et al. Therapeutic potential and critical analysis of trastuzumab and bevacizumab in combination with different chemotherapeutic agents against metastatic breast/colorectal cancer affecting various endpoints. Crit Rev Oncol Hematol 2016;104:124-30.
Lambrechts D, Lenz H-J, de Haas S, Carmeliet P, Scherer SJ. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 2013;31:1219-30.
Cremolini C, Del Re M, Antoniotti C, Lonardi S, Bergamo F, Loupakis F, et al. DPYD and UGT1A1 genotyping to predict adverse events during first-line FOLFIRI or FOLFOXIRI plus bevacizumab in metastatic colorectal cancer. Oncotarget 2018;9:7859.
Pentheroudakis G, Mavroeidis L, Papadopoulou K, Koliou G-A, Bamia C, Chatzopoulos K, et al. Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab. Clin Colorectal Cancer 2019;18:e370-84.
Aprile G, Bonotto M, Ongaro E, Pozzo C, Giuliani F. Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from benchside to clinical use. Drugs 2013;73:2003-15.
Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol 2015;16:499-508.
Obermannová R, Lordick F. Insights into next developments in advanced gastric cancer. Curr Opin Oncol 2016;28:367-75.
Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausová J, Macarulla T, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012;30:3499-506.
Li D, Xie K, Ding G, Li J, Chen K, Li H, et al. Tumor resistance to anti-VEGF therapy through up-regulation of VEGF-C expression. Cancer Lett 2014;346:45-52.
Majithia N, Grothey A. Regorafenib in the treatment of colorectal cancer. Expert Opin Pharmacother 2016;17:137-45.
Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381:303-12.
Mirone G, Perna S, Shukla A, Marfe G. Involvement of Notch‐1 in Resistance to Regorafenib in Colon Cancer Cells. J Cell Physiol 2016;231:1097-105.
Van Cutsem E, Köhne C-H, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009;360:1408-17.
Van Emburgh BO, Sartore-Bianchi A, Di Nicolantonio F, Siena S, Bardelli A. Acquired resistance to EGFR-targeted therapies in colorectal cancer. Mol Oncol 2014;8:1084-94.
Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol 2014;15:569-79.
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010;11:753-62.
Sood A, McClain D, Maitra R, Basu-Mallick A, Seetharam R, Kaubisch A, et al. PTEN gene expression and mutations in the PIK3CA gene as predictors of clinical benefit to anti-epidermal growth factor receptor antibody therapy in patients with KRAS wild-type metastatic colorectal cancer. Clin Colorectal Cancer 2012;11:143-50.
Pohl M, Schmiegel W. Therapeutic strategies in diseases of the digestive tract-2015 and beyond targeted therapies in colon cancer today and tomorrow. Dig Dis 2016;34:574-9.
Richman SD, Southward K, Chambers P, Cross D, Barrett J, Hemmings G, et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. J Pathol 2016;238:562-70.
Inno A, Di Salvatore M, Cenci T, Martini M, Orlandi A, Strippoli A, et al. Is there a role for IGF1R and c-MET pathways in resistance to cetuximab in metastatic colorectal cancer? Clin Colorectal Cancer 2011;10:325-32.
Abdollahpour-Alitappeh M, Lotfinia M, Gharibi T, Mardaneh J, Farhadihosseinabadi B, Larki P, et al. Antibody-drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes. J Cell Physiol 2019;234:5628-5642.
Rezaei-Tavirani M, Safaei A, Zali MR. The association between polymorphismsin insulin and obesity related genesand risk of colorectal cancer. Iran J Cancer Prev 2013;6:179.
Douillard J-Y, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clini Oncol 2010;28:4697-705.
Wilson PM, Danenberg PV, Johnston PG, Lenz H-J, Ladner RD. Standing the test of time: targeting thymidylate biosynthesis in cancer therapy. Nat Rev Clin Oncol 2014;11:282.
Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003;3:330.
Qiu LX, Tang QY, Bai JL, Qian XP, Li RT, Liu BR, et al. Predictive value of thymidylate synthase expression in advanced colorectal cancer patients receiving fluoropyrimidine‐based chemotherapy: evidence from 24 studies. Int J Cancer 2008;123:2384-9.
Etienne‐Grimaldi MC, Milano G, Maindrault‐Gœbel F, Chibaudel B, Formento JL, Francoual M, et al. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and FOLFOX response in colorectal cancer patients. Br J Clin Pharmacol 2010;69:58-66.
Panczyk M. Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years. World J Gastroenterol 2014;20:9775.
Koopman M, Venderbosch S, van Tinteren H, Ligtenberg MJ, Nagtegaal I, Van Krieken JH, et al. Predictive and prognostic markers for the outcome of chemotherapy in advanced colorectal cancer, a retrospective analysis of the phase III randomised CAIRO study. Eur J Cancer 2009;45:1999-2006.
Vallböhmer D, Kuramochi H, Shimizu D, Danenberg KD, Lindebjerg J, Nielsen JN, et al. Molecular factors of 5-fluorouracil metabolism in colorectal cancer: analysis of primary tumor and lymph node metastasis. Int J Oncol 2006;28:527-33.
Kim S, Hong Y, Shim E, Kong S, Shin A, Baek J, et al. S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis. Br J Cancer 2013;109:1420.
Baba H, Watanabe M, Okabe H, Miyamoto Y, Sakamoto Y, Baba Y, et al. Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer. Br J Cancer 2012;107:1950.
Moutinho C, Martinez-Cardús A, Santos C, Navarro-Pérez V, Martínez-Balibrea E, Musulen E, et al. Epigenetic inactivation of the BRCA1 interactor SRBC and resistance to oxaliplatin in colorectal cancer. J Natl Cancer Inst 2014;106.
Zamanian-Azodi M, Rezaei-Tavirani M, Rahmati-Rad S, Hasanzadeh H, Tavirani MR, Seyyedi SS. Protein-Protein Interaction Network could reveal the relationship between the breast and colon cancer. Gastroenterol Hepatol Bed Bench 2015;8:215.
Goudarzi M, Goudarzi H, Alebouyeh M, Azimi Rad M, Shayegan Mehr FS, Zali MR, et al. Antimicrobial susceptibility of clostridium difficile clinical isolates in iran. Iran Red Crescent Med J 2013;15:704-11.
Boyer J, McLean EG, Aroori S, Wilson P, McCulla A, Carey PD, et al. Characterization of p53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin, and irinotecan. Clin Cancer Res 2004;10:2158-67.
Longley D, Johnston P. Molecular mechanisms of drug resistance. J Pathol 2005;205:275-92.
Zhao J, Li W, Zhu D, Yu Q, Zhang Z, Sun M, et al. Association of single nucleotide polymorphisms in MTHFR and ABCG2 with the different efficacy of first-line chemotherapy in metastatic colorectal cancer. Med Oncol 2014;31:802.
Nygård SB, Christensen IJ, Nielsen SL, Nielsen HJ, Brünner N, Spindler K-LG. Assessment of the topoisomerase I gene copy number as a predictive biomarker of objective response to irinotecan in metastatic colorectal cancer. Scand J Gastroenterol 2013;49:84-91.
Gongora C, Vezzio-Vie N, Tuduri S, Denis V, Causse A, Auzanneau C, et al. New Topoisomerase I mutations are associated with resistance to camptothecin. Mol Cancer 2011;10:64.
Ma CJ, Huang CW, Chang TK, Tsai HL, Su WC, Yeh YS, et al. Oncologic Outcomes in Metastatic Colorectal Cancer with Regorafenib with FOLFIRI as a Third-or Fourth-Line Setting. Transl Oncol 2019;12:502-12.
- Abstract Viewed: 0 times
- PDF Downloaded: 0 times