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

  • Romain Cohen
  • Magali Svrcek
  • Chantal Dreyer
  • Pascale Cervera
  • Alex Duval
  • Marc Pocard
  • Jean-François Fléjou
  • Aimery de Gramont
  • Thierry AndréEmail author
Gastrointestinal Cancers (J Meyer, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Gastrointestinal Cancers

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

Microsatellite instability BRAF mutation Immune checkpoint PD-1 PD-L1 

Notes

Acknowledgments

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.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of outstanding importance

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Romain Cohen
    • 1
  • Magali Svrcek
    • 2
    • 3
  • Chantal Dreyer
    • 1
  • Pascale Cervera
    • 2
    • 3
  • Alex Duval
    • 4
  • Marc Pocard
    • 5
    • 6
  • Jean-François Fléjou
    • 2
    • 3
  • Aimery de Gramont
    • 5
    • 7
  • Thierry André
    • 1
    • 3
    • 4
    • 5
    Email author
  1. 1.Department of Medical OncologyHospital Saint-Antoine, Assistance publique-Hôpitaux de ParisParisFrance
  2. 2.Department of PathologyHospital Saint-Antoine, APHPParisFrance
  3. 3.University Pierre et Marie Curie (UMPC)ParisFrance
  4. 4.INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-AntoineEquipe “Instabilité des Microsatellites et Cancers,” Equipe labellisée par la Ligue Nationale contre le CancerParisFrance
  5. 5.GERCOR, Oncology Multidisciplinary GroupParisFrance
  6. 6.Departement of Digestive and Oncologic SurgeryHospital Lariboisière, APHPParisFrance
  7. 7.Department of Medical OncologyInstitut Hospitalier Franco-BritanniqueLevallois-PerretFrance

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