New Therapeutic Opportunities Based on DNA Mismatch Repair and BRAF Status in Metastatic Colorectal Cancer
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Recently, colorectal cancer (CRC) subtyping consortium identified four consensus molecular subtypes (CMS1–4). CMS1 is enriched for deficient mismatch repair (dMMR) and BRAF V600E tumors. Intriguingly, this subtype has better relapse-free survival but worse overall survival after relapse compared with the other subtypes. Growing evidence is accumulating on the benefit of specific therapeutic strategies such as immune checkpoint inhibition therapy in dMMR tumors and mitogen-activated protein kinase (MAPK) pathway targeted therapy in tumors harboring BRAF V600E mutation. After reviewing dMMR prognostic value, immune checkpoints as major targets for dMMR carcinomas will be highlighted. Following, BRAF V600E prognostic impact will be reviewed and therapeutic strategies with the combination of cytotoxic agents and especially the combinations of BRAF and MAPK inhibitors will be discussed.
KeywordsMicrosatellite instability BRAF mutation Immune checkpoint PD-1 PD-L1
Authors would like to thank Magdalena Benetkiewicz for reviewing/editorial assistance.
Compliance with Ethical Standards
Conflict of Interest
Romain Cohen declares that he has no conflict of interest.
Magali Svrcek declares that she has no conflict of interest.
Chantal Dreyer declares that she has no conflict of interest.
Pascale Cervera declares that he has no conflict of interest.
Alex Duval declares that he has no conflict of interest.
Marc Pocard declares that he has no conflict of interest.
Jean-François Fléjou declares that he has no conflict of interest.
Aimery de Gramont has received compensation from Roche for service on advisory boards and from Sanofi for the attendance of meetings.
Thierry André is principal investigator for studies in metastatic colorectal cancer sponsored by Bristol-Myers Squibb, Novartis, and Roche and has received compensation from Roche, Amgen, and Bristol-Myers Squibb for service as a consultant.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of outstanding importance
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