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.

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.