Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 24, 2021; 12(11): 1000-1008
Published online Nov 24, 2021. doi: 10.5306/wjco.v12.i11.1000
Consensus molecular subtypes of colorectal cancer in clinical practice: A translational approach
Guillermo Valenzuela, Joaquín Canepa, Carolina Simonetti, Loreto Solo de Zaldívar, Katherine Marcelain, Jaime González-Montero
Guillermo Valenzuela, Joaquín Canepa, Carolina Simonetti, Loreto Solo de Zaldívar, Katherine Marcelain, Jaime González-Montero, Basic and Clinical Oncology Department, University of Chile, Santiago 8380453, Chile
Author contributions: Valenzuela G wrote this manuscript, created figures and tables; Canepa J, Solo de Zaldívar L, Simonetti C, Marcelain K, and González-Montero J collected data and references and critically revised the manuscript; all authors approved the final version of the manuscript for publication.
Supported by Agencia Nacional de Investigación y Desarrollo de Chile, Fondo Nacional de Investigación y Desarrollo en Salud, FONIS, No. SA20I0059.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Jaime González-Montero, MD, PhD, Assistant Professor, Doctor, Basic and Clinical Oncology Department, University of Chile, Independencia 1027, Casilla 70058, Santiago 8380453, Chile.
Received: June 24, 2021
Peer-review started: June 24, 2021
First decision: August 8, 2021
Revised: August 11, 2021
Accepted: September 19, 2021
Article in press: September 19, 2021
Published online: November 24, 2021

The identification of several genetic mutations in colorectal cancer (CRC) has allowed a better comprehension of the prognosis and response to different antineoplastic treatments. Recently, through a systematic process, consensus molecular subtypes (CMS) have been described to characterize genetic and molecular mutations in CRC patients. Through CMS, CRC patients can be categorized into four molecular subtypes of CRC by wide transcriptional genome analysis. CMS1 has microsatellite instability and mutations in CIMP and BRAF pathways. CMS2, distinguished by mutations in specific pathways linked to cellular metabolism, also has a better prognosis. CMS3 has a KRAS mutation as a hallmark. CMS4 presents mutations in fibrogenesis pathways and mesenchymal-epithelial transition, associated with a worse prognosis. CMS classification can be a meaningful step in providing possible answers to important issues in CRC, such as the use of adjuvant chemotherapy in stage II, personalized first-line chemotherapy for metastasic CRC, and possible new target treatments that address specific pathways in each molecular subtype. Understanding CMS is a crucial step in personalized medicine, although prospective clinical trials selecting patients by CMS are required to pass proof-of-concept before becoming a routine clinical tool in oncology routine care.

Keywords: Colorectal neoplasms, Precision medicine, Microsatellite instability, Next-generation sequencing

Core Tip: Colorectal cancer has a variable response to different treatments that could be explained by genetic and molecular heterogeneity in the neoplasm. Recently, a novel classification according to consensus molecular subtype has been proposed to explain this neoplasm heterogeneity. From a clinical oncology perspective, this classification opens opportunities to resolve some current clinical questions in the treatment of colorectal cancer.