{"entity":{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","aka":[],"tldr":"The consensus molecular subtypes are four gene-expression groups of bowel cancer: immune (CMS1), canonical (CMS2), metabolic (CMS3), and mesenchymal (CMS4), with different prognoses.","summary":"The consensus molecular subtypes divide colorectal cancer into four gene-expression groups defined by Guinney and colleagues in Nature Medicine in 2015. CMS1 is the immune subtype, enriched for microsatellite instability and BRAF mutation; CMS2 is the canonical WNT and MYC subtype; CMS3 is the metabolic, KRAS-associated subtype; and CMS4 is the mesenchymal, TGF-beta and stroma-rich subtype with the worst prognosis. The classification is prognostic and partly predictive, with CMS2 appearing to gain most from anti-EGFR therapy, but it is not yet used routinely in the clinic. Readers meet it through RNA sequencing, the Wnt, epithelial-mesenchymal transition and mismatch repair pathways, and the idea of matching therapy to the type of scar-forming cell in a tumour.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer","links":[{"label":"The consensus molecular subtypes of colorectal cancer (Guinney et al., Nature Medicine 2015)","url":"https://doi.org/10.1038/nm.3967"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt","emt"],"terms":["serrated-pathway","adenoma-carcinoma-sequence","sidedness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cms-guinney-nat-med-2015","paper-lenz-cms-calgb-swog-80405-jco-2019","paper-isella-stromal-contribution-colorectal-transcriptome-nat-genet-2015","paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015","paper-loree-tumour-location-continuum-colorectal-ccr-2018"],"journals":[],"dependsOn":[],"notes":["What the four classes are worth in practice. In the one randomised test, on 581 CALGB/SWOG 80405 patients, the subtypes were both prognostic and predictive: CMS1 patients lived longer on bevacizumab than cetuximab and CMS2 patients longer on cetuximab than bevacizumab (Lenz 2019). But the mesenchymal CMS4 signal comes from the stroma rather than the cancer cells, shown by species-specific expression analysis in patient-derived xenografts (Isella 2015) and by the finding that every poor-prognosis subtype shares one TGF-beta-induced stromal programme (Calon 2015), so a CMS4 call partly measures how much stroma was in the block. The classes also shift continuously along the bowel, CMS1 and CMS3 falling and CMS2 rising distally (Loree 2018). No guideline uses the classification and no assay is approved for it.","The shares, from the consortium paper that defined them: CMS1 (microsatellite instability immune) 14 percent, hypermutated with strong immune activation; CMS2 (canonical) 37 percent, epithelial with marked WNT and MYC signalling; CMS3 (metabolic) 13 percent, epithelial with metabolic dysregulation; CMS4 (mesenchymal) 23 percent, with transforming growth factor beta activation, stromal invasion and angiogenesis. A further 13 percent of samples had mixed features, read as a transition phenotype or as heterogeneity within one tumour (Guinney 2015)."],"category":"Genomics & genetics"},"route":"/terms/cms-subtypes/","neighbours":{"cancer":[{"id":"braf-v600e-colorectal","kind":"cancer","name":"BRAF V600E-mutant colorectal cancer","route":"/cancers/braf-v600e-colorectal/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"pathway":[{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","route":"/pathways/emt/"},{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"adenoma-carcinoma-sequence","kind":"term","name":"Adenoma-carcinoma sequence","route":"/terms/adenoma-carcinoma-sequence/"},{"id":"cimp","kind":"term","name":"CpG island methylator phenotype (CIMP)","route":"/terms/cimp/"},{"id":"immunoscore","kind":"term","name":"Immunoscore","route":"/terms/immunoscore/"},{"id":"rspo-fusion","kind":"term","name":"R-spondin fusion","route":"/terms/rspo-fusion/"},{"id":"serrated-pathway","kind":"term","name":"Serrated pathway","route":"/terms/serrated-pathway/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}],"paper":[{"id":"paper-loree-tumour-location-continuum-colorectal-ccr-2018","kind":"paper","name":"Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes","route":"/key-papers/paper-loree-tumour-location-continuum-colorectal-ccr-2018/"},{"id":"paper-lenz-cms-calgb-swog-80405-jco-2019","kind":"paper","name":"Impact of consensus molecular subtype on survival in patients with metastatic colorectal cancer: results from CALGB/SWOG 80405","route":"/key-papers/paper-lenz-cms-calgb-swog-80405-jco-2019/"},{"id":"paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","kind":"paper","name":"Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials","route":"/key-papers/paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017/"},{"id":"paper-isella-stromal-contribution-colorectal-transcriptome-nat-genet-2015","kind":"paper","name":"Stromal contribution to the colorectal cancer transcriptome","route":"/key-papers/paper-isella-stromal-contribution-colorectal-transcriptome-nat-genet-2015/"},{"id":"paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015","kind":"paper","name":"Stromal gene expression defines poor-prognosis subtypes in colorectal cancer","route":"/key-papers/paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015/"},{"id":"paper-cms-guinney-nat-med-2015","kind":"paper","name":"The consensus molecular subtypes of colorectal cancer","route":"/key-papers/paper-cms-guinney-nat-med-2015/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"}],"idea":[{"id":"idea-bio2-caf-subtype-assignment","kind":"idea","name":"Match therapy to the type of scar-forming cell in the tumour","route":"/ideas/idea-bio2-caf-subtype-assignment/"},{"id":"idea-crc-mss-immunotherapy-by-biomarker-not-by-line","kind":"idea","name":"Select microsatellite stable patients for immunotherapy by a measured immune biomarker, not by how many treatments they have already failed","route":"/ideas/idea-crc-mss-immunotherapy-by-biomarker-not-by-line/"}],"trial":[{"id":"petacc-3","kind":"trial","name":"PETACC-3","route":"/trials/petacc-3/"}]}}