Consensus molecular subtypes of colorectal cancer in clinical practice: A translational approach

Abstract

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.

The Role of Tumor Microenvironment and Immune Response in Colorectal Cancer Development and Prognosis

“…Understanding CMS is a crucial step towards personalized medicine as it could optimize the management of individual patients. For example, it will allow defining the best first-line chemotherapy regimen (poor efficiency of oxaliplatin in CMS1 and CMS4) or application of immunotherapy for metastatic CRC in CMS4 patients ( 127 ).…”

Comprehensive exploration of tumor immune microenvironment feature and therapeutic response in colorectal cancer based on a novel immune-related long non-coding RNA prognostic signature

“…There are four types of CMS, including microsatellite stable (MSS) and immune activation type (CMS1), classic colorectal cancer type (CMS2), metabolic type (CMS3) and interstitial type (CMS4). CMS typing has been studied all over the world, but it has not been widely recognized and accepted, and its guiding role in clinical practice is limited ( Valenzuela et al, 2021 ). Therefore, it is of great significance to explore accurate and reliable biomarkers to predict the prognosis for the individualized treatment of CRC patients.…”

Identifying Essential Genes in Genome-Scale Metabolic Models of Consensus Molecular Subtypes of Colorectal Cancer

“…Molecular subtype-based therapies provide a new framework for implementing preferred and precise medical treatments. Several studies have used CMS classification to predict the prognosis of a patient with CRC and determine treatment strategies for the patient [3][4][5][6][7][8][9]. Tissue-specific genome-scale metabolic models (GSMM) are applied to identify anticancer targets and provide detailed insights into the metabolic bases of physiological and pathological processes .…”