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

  • Gastrointestinal Cancers (J Meyer, Section Editor)
  • Published:
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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.

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Acknowledgments

Authors would like to thank Magdalena Benetkiewicz for reviewing/editorial assistance.

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Authors and Affiliations

  1. Department of Medical Oncology, Hospital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012, Paris, France

    Romain Cohen, Chantal Dreyer & Thierry André

  2. Department of Pathology, Hospital Saint-Antoine, APHP, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France

    Magali Svrcek, Pascale Cervera & Jean-François Fléjou

  3. University Pierre et Marie Curie (UMPC), Paris VI, 4 Place Jussieu, Paris, 75005, France

    Magali Svrcek, Pascale Cervera, Jean-François Fléjou & Thierry André

  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

    Alex Duval & Thierry André

  5. GERCOR, Oncology Multidisciplinary Group, 151 rue du Faubourg Saint Antoine, Paris, 75011, France

    Marc Pocard, Aimery de Gramont & Thierry André

  6. Departement of Digestive and Oncologic Surgery, Hospital Lariboisière, APHP, 2 rue Ambroise Paré, Paris, 75010, France

    Marc Pocard

  7. Department of Medical Oncology, Institut Hospitalier Franco-Britannique, 4 rue Kléber, 92300, Levallois-Perret, France

    Aimery de Gramont

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  1. Romain Cohen
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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.

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Cohen, R., Svrcek, M., Dreyer, C. et al. New Therapeutic Opportunities Based on DNA Mismatch Repair and BRAF Status in Metastatic Colorectal Cancer. Curr Oncol Rep 18, 18 (2016). https://doi.org/10.1007/s11912-016-0504-2

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  • DOI: https://doi.org/10.1007/s11912-016-0504-2

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