Molecular Subtypes of Colorectal Cancer: An emerging Therapeutic Opportunity for Personalized Medicine

Overview

Journal Genes Dis

Date 2021 May 17

PMID 33997160

Citations 55

Authors

Manish Pratap Singh

Sandhya Rai

Ashutosh Pandey

Nand K Singh

Sameer Srivastava

Affiliations

Soon will be listed here.

Abstract

Molecular subtypes-based therapies offer new potential framework for desired and precise outcome in clinical settings. Current treatment strategies in colorectal cancer are largely 'one drug fit all' model for patients that display same pathological conditions. However, CRC is a very heterogenous set of malignancy that does not support for above criteria. Each subtype displays different pathological and genetic signatures. Based on these features, therapeutic stratification for individual patients may be designed, which may ultimately lead to improved therapeutic outcomes. In this comprehensive review, we have attempted to briefly outline major CRC pathways. A detailed overview of molecular subtypes and their clinical significance has been discussed. Present and future methods, governing CRC subtyping in the era of personalized therapy with a special emphasis on CMS subtypes of CRC has been reviewed. Together, discovery and validation of new CRC patient stratification methods, screening for novel therapeutic targets, and enhanced diagnosis of CRC may improve the treatment outcome.

Citing Articles

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From Subtypes to Solutions: Integrating CMS Classification with Precision Therapeutics in Colorectal Cancer.

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LincROR promotes tumor growth of colorectal cancer through the miR-145/WNT2B/WNT10A/Wnt/β-catenin regulatory axis.

Deng L, Li S, Xie T, Zeng W, Wang Y, Shi C PLoS One. 2024; 19(11):e0312417.

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High α-SMA expression in the tumor stroma is associated with adverse clinical parameters in mismatch repair-proficient colorectal cancers only.

Sculthorpe D, Denton A, Fadhil W, Rusnita D, Ilyas M, Mukherjee A Am J Clin Pathol. 2024; 163(3):464-472.

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References

Esteller M, Corn P, Baylin S, Herman J . A gene hypermethylation profile of human cancer. Cancer Res. 2001; 61(8):3225-9. View

Ciardiello F, Normanno N, Martinelli E, Troiani T, Pisconti S, Cardone C . Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX. Ann Oncol. 2016; 27(6):1055-1061. DOI: 10.1093/annonc/mdw136. View

Le D, Durham J, Smith K, Wang H, Bartlett B, Aulakh L . Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357(6349):409-413. PMC: 5576142. DOI: 10.1126/science.aan6733. View

Marisa L, De Reynies A, Duval A, Selves J, Gaub M, Vescovo L . Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med. 2013; 10(5):e1001453. PMC: 3660251. DOI: 10.1371/journal.pmed.1001453. View

Guinney J, Dienstmann R, Wang X, De Reynies A, Schlicker A, Soneson C . The consensus molecular subtypes of colorectal cancer. Nat Med. 2015; 21(11):1350-6. PMC: 4636487. DOI: 10.1038/nm.3967. View

Park J, Powell A, Roxburgh C, Horgan P, McMillan D, Edwards J . Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment. Br J Cancer. 2016; 114(5):562-70. PMC: 4782207. DOI: 10.1038/bjc.2016.17. View

Seshagiri S, Stawiski E, Durinck S, Modrusan Z, Storm E, Conboy C . Recurrent R-spondin fusions in colon cancer. Nature. 2012; 488(7413):660-4. PMC: 3690621. DOI: 10.1038/nature11282. View

Sinicrope F, Mahoney M, Smyrk T, Thibodeau S, Warren R, Bertagnolli M . Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol. 2013; 31(29):3664-72. PMC: 3789216. DOI: 10.1200/JCO.2013.48.9591. View

Deschoolmeester V, Baay M, Lardon F, Pauwels P, Peeters M . Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI. Cancer Microenviron. 2011; 4(3):377-92. PMC: 3234325. DOI: 10.1007/s12307-011-0068-5. View

10.

Staudacher J, Bauer J, Jana A, Tian J, Carroll T, Mancinelli G . Activin signaling is an essential component of the TGF-β induced pro-metastatic phenotype in colorectal cancer. Sci Rep. 2017; 7(1):5569. PMC: 5514149. DOI: 10.1038/s41598-017-05907-8. View

11.

Hagland H, Berg M, Jolma I, Carlsen A, Soreide K . Molecular pathways and cellular metabolism in colorectal cancer. Dig Surg. 2013; 30(1):12-25. DOI: 10.1159/000347166. View

12.

Paul Singh P, Sharma P, Krishnan G, Lockhart A . Immune checkpoints and immunotherapy for colorectal cancer. Gastroenterol Rep (Oxf). 2015; 3(4):289-97. PMC: 4650981. DOI: 10.1093/gastro/gov053. View

13.

Ogino S, Nosho K, Kirkner G, Kawasaki T, Meyerhardt J, Loda M . CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut. 2008; 58(1):90-6. PMC: 2679586. DOI: 10.1136/gut.2008.155473. View

14.

Toyota M, Ahuja N, Herman J, Baylin S, Issa J . CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999; 96(15):8681-6. PMC: 17576. DOI: 10.1073/pnas.96.15.8681. View

15.

Graham D, Coyle V, Kennedy R, Wilson R . Molecular Subtypes and Personalized Therapy in Metastatic Colorectal Cancer. Curr Colorectal Cancer Rep. 2016; 12:141-150. PMC: 4879165. DOI: 10.1007/s11888-016-0312-y. View

16.

De Smedt L, Lemahieu J, Palmans S, Govaere O, Tousseyn T, Van Cutsem E . Microsatellite instable vs stable colon carcinomas: analysis of tumour heterogeneity, inflammation and angiogenesis. Br J Cancer. 2015; 113(3):500-9. PMC: 4522625. DOI: 10.1038/bjc.2015.213. View

17.

Phipps A, Buchanan D, Makar K, Win A, Baron J, Lindor N . KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers. Br J Cancer. 2013; 108(8):1757-64. PMC: 3668469. DOI: 10.1038/bjc.2013.118. View

18.

Le D, Uram J, Wang H, Bartlett B, Kemberling H, Eyring A . PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015; 372(26):2509-20. PMC: 4481136. DOI: 10.1056/NEJMoa1500596. View

19.

Park J, Richards C, McMillan D, Horgan P, Roxburgh C . The relationship between tumour stroma percentage, the tumour microenvironment and survival in patients with primary operable colorectal cancer. Ann Oncol. 2014; 25(3):644-651. PMC: 4433525. DOI: 10.1093/annonc/mdt593. View

20.

Chen X, Li L, Jiang J, Li K, Su Z, Zhang F . Propofol elicits autophagy via endoplasmic reticulum stress and calcium exchange in C2C12 myoblast cell line. PLoS One. 2018; 13(5):e0197934. PMC: 5967754. DOI: 10.1371/journal.pone.0197934. View