Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Oct 30;8(2):133-145.
doi: 10.1016/j.gendis.2019.10.013. eCollection 2021 Mar.

Molecular subtypes of colorectal cancer: An emerging therapeutic opportunity for personalized medicine

Manish Pratap Singh  1 , Sandhya Rai  1 , Ashutosh Pandey  1 , Nand K Singh  1 , Sameer Srivastava  1
Affiliations
Review

Molecular subtypes of colorectal cancer: An emerging therapeutic opportunity for personalized medicine

Manish Pratap Singh et al. Genes Dis. .

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.

Keywords: Biomarkers; CMS subtypes; Immunotherapy; Molecular screening; Personalized medicine.

PubMed Disclaimer

Figures

Figure 1
Figure 1
CMS classification of colorectal cancer: Major characteristics of consensus molecular subtypes in CRC. Each group is elaborated with its special features and clinical significance. Currently, CRC is subdivided in to four primary major classes and one mixed subtype. CMS 1 tumor display a higher percentage of MSI, hypermethylation, and hypermutation, and associated with improved survival. CMS2; These contributes to larger subset of subtypes approximately 37% of all tumor subtypes. These tumors have SCNA high, microsatellite stable, activated WNT & Myc pathway and elevated EGFR with mutated TP53 gene. CMS 3 tumors harbors high mutation in KRAS gene and KRAS mutation is highly heterogenous at the gene expression level and having epithelial characteristics. CMS 4 has a high CpG methylator phenotype with strong stromal infiltration, upregulated angiogenic features and hyperactivated TGF-beta.
Figure 2
Figure 2
A proposed flow chart of therapeutic settings and major bottleneck factors in CRC personalized therapy: Personalized therapy for CRC patients follows a route from primary screening to molecular testing that ultimately provide a precise information to clinical team in therapy selection. The first step is the patient approches to the clinician and checked for disease symptoms in pathology. The sample then screened for molecular testing to check molecular profile of specific tumors. Then, pathology and molecular test reports are analyzed by the team of clinician and therapy for a particular patient have to be decided on the basis of pervious data available from research and outcome given by the various drugs of interest (Red arrow indicates up line of screening and diagnosis while green line represents reports of the tests that leads toward the treatment team). This personalized treatment flow faces several hurdles that have to be overcome in future treatment management to improve the therapeutic outcome.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin. 2018;68(6):394–424. - PubMed
    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019. CA: A Cancer J Clin. 2019;69(1):7–34. - PubMed
    1. Nakayama G., Tanaka C., Kodera Y. Current options for the diagnosis, staging and therapeutic management of colorectal cancer. Gastrointest Tumours. 2013;1(1):25–32. - PMC - PubMed
    1. Zhao B., Wang L., Qiu H. Mechanisms of resistance to anti-EGFR therapy in colorectal cancer. OncoTarget. 2016;8(3):3980–4000. - PMC - PubMed
    1. Misale S., Di Nicolantonio F., Sartore-Bianchi A., Siena S., Bardelli A. Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution. Cancer Discov. 2014;4(11):1269–1280. - PubMed

LinkOut - more resources