title: New Therapeutic Opportunities Based on DNA Mismatch Repair and BRAF Status in Metastatic Colorectal Cancer.
abstract: 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.
authors: Department of Medical Oncology, Hospital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012, Paris, France.
authors: Romain
authors: R
authors: Cohen
authors: Department of Pathology, Hospital Saint-Antoine, APHP, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France.|University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France.
authors: Magali
authors: M
authors: Svrcek
authors: Department of Medical Oncology, Hospital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012, Paris, France.
authors: Chantal
authors: C
authors: Dreyer
authors: Department of Pathology, Hospital Saint-Antoine, APHP, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France.|University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France.
authors: Pascale
authors: P
authors: Cervera
authors: INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe "Instabilité des Microsatellites et Cancers," Equipe labellisée par la Ligue Nationale contre le Cancer, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France.
authors: Alex
authors: A
authors: Duval
authors: GERCOR, Oncology Multidisciplinary Group, 151 rue du Faubourg Saint Antoine, Paris, 75011, France.|Departement of Digestive and Oncologic Surgery, Hospital Lariboisière, APHP, 2 rue Ambroise Paré, Paris, 75010, France.
authors: Marc
authors: M
authors: Pocard
authors: Department of Pathology, Hospital Saint-Antoine, APHP, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France.|University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France.
authors: Jean-François
authors: JF
authors: Fléjou
authors: GERCOR, Oncology Multidisciplinary Group, 151 rue du Faubourg Saint Antoine, Paris, 75011, France.|Department of Medical Oncology, Institut Hospitalier Franco-Britannique, 4 rue Kléber, 92300, Levallois-Perret, France.
authors: Aimery
authors: A
authors: de Gramont
authors: Department of Medical Oncology, Hospital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012, Paris, France. thierry.andre@aphp.fr.|University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France. thierry.andre@aphp.fr.|INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe "Instabilité des Microsatellites et Cancers," Equipe labellisée par la Ligue Nationale contre le Cancer, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France. thierry.andre@aphp.fr.|GERCOR, Oncology Multidisciplinary Group, 151 rue du Faubourg Saint Antoine, Paris, 75011, France. thierry.andre@aphp.fr.
authors: Thierry
authors: T
authors: André
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D053843:DNA Mismatch Repair; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutation; Immune checkpoint; Microsatellite instability; PD-1; PD-L1