Review

. 2016 Mar;18(3):18.

doi: 10.1007/s11912-016-0504-2.

New Therapeutic Opportunities Based on DNA Mismatch Repair and BRAF Status in Metastatic Colorectal Cancer

Romain Cohen¹, Magali Svrcek^{2

3}, Chantal Dreyer¹, Pascale Cervera^{2

3}, Alex Duval⁴, Marc Pocard^{5

6}, Jean-François Fléjou^{2

3}, Aimery de Gramont^{5

7}, Thierry André^{8

9

10

11}

Affiliations

¹ Department of Medical Oncology, Hospital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012, Paris, France.
² Department of Pathology, Hospital Saint-Antoine, APHP, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France.
³ University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France.
⁴ 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.
⁵ GERCOR, Oncology Multidisciplinary Group, 151 rue du Faubourg Saint Antoine, Paris, 75011, France.
⁶ Departement of Digestive and Oncologic Surgery, Hospital Lariboisière, APHP, 2 rue Ambroise Paré, Paris, 75010, France.
⁷ Department of Medical Oncology, Institut Hospitalier Franco-Britannique, 4 rue Kléber, 92300, Levallois-Perret, France.
⁸ 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.
⁹ University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France. thierry.andre@aphp.fr.
¹⁰ 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.
¹¹ GERCOR, Oncology Multidisciplinary Group, 151 rue du Faubourg Saint Antoine, Paris, 75011, France. thierry.andre@aphp.fr.

PMID: 26861657
DOI: 10.1007/s11912-016-0504-2

Review

New Therapeutic Opportunities Based on DNA Mismatch Repair and BRAF Status in Metastatic Colorectal Cancer

Romain Cohen et al. Curr Oncol Rep. 2016 Mar.

. 2016 Mar;18(3):18.

doi: 10.1007/s11912-016-0504-2.

Authors

Affiliations

¹ Department of Medical Oncology, Hospital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012, Paris, France.
² Department of Pathology, Hospital Saint-Antoine, APHP, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France.
³ University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France.
⁴ 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.
⁵ GERCOR, Oncology Multidisciplinary Group, 151 rue du Faubourg Saint Antoine, Paris, 75011, France.
⁶ Departement of Digestive and Oncologic Surgery, Hospital Lariboisière, APHP, 2 rue Ambroise Paré, Paris, 75010, France.
⁷ Department of Medical Oncology, Institut Hospitalier Franco-Britannique, 4 rue Kléber, 92300, Levallois-Perret, France.
⁸ 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.
⁹ University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France. thierry.andre@aphp.fr.
¹⁰ 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.
¹¹ GERCOR, Oncology Multidisciplinary Group, 151 rue du Faubourg Saint Antoine, Paris, 75011, France. thierry.andre@aphp.fr.

PMID: 26861657
DOI: 10.1007/s11912-016-0504-2

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.

Keywords: BRAF mutation; Immune checkpoint; Microsatellite instability; PD-1; PD-L1.

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New Therapeutic Opportunities Based on DNA Mismatch Repair and BRAF Status in Metastatic Colorectal Cancer

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