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Cancer therapy

Seeking therapeutic synergy in BRAF mutant colorectal cancer

Nature Medicine volume 29, pages 307–308 (2023)Cite this article

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In a phase I trial, the combination of dabrafenib, trametinib and spartalizumab uncovers the crosstalk between the MAPK pathway and the immune system, which offers a promising new strategy to improve clinical outcomes.

The BRAFV600E mutation is the most frequent alteration in the BRAF oncogene and is present in multiple tumor types, at a variable frequency — causing constitutive activation of BRAF and aberrant cell proliferation, invasion and spreading. In metastatic colorectal cancer (mCRC), the BRAFV600E mutation occurs in up to 10% of patients and is associated with poor prognosis1; however, BRAF inhibition as monotherapy has yielded poor clinical activity in patients with mCRC2.

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Fig. 1: BRAF pathway and targeted agents.

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Authors and Affiliations

  1. Medical Oncology Department, Vall d’Hebron Hospital Campus and Institute of Oncology (VHIO), Barcelona, Spain

    Elena Elez, Javier Ros & Josep Tabernero

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  1. Elena Elez
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  2. Javier Ros
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  3. Josep Tabernero
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Correspondence to Elena Elez.

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Competing interests

E.E. has received personal speaker honoraria from Organon and Novartis; and personal advisory board honoraria from Amgen, Bayer, Hoffman-La Roche, Merck Serono, Sanofi, Pierre Fabre, MSD, and Servier. Educational collaboration with Imedex/HMP and PeerView Institute for Medical Education. J.R. has received personal speaker honoraria from Sanofi and AMGEN, and accommodation expenses from Pierre-Fabre, Servier, Amgen and Merck. J.T. reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics and TheraMyc. Stocks: Oniria Therapeutics and also educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER).

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Elez, E., Ros, J. & Tabernero, J. Seeking therapeutic synergy in BRAF mutant colorectal cancer. Nat Med 29, 307–308 (2023). https://doi.org/10.1038/s41591-022-02192-5

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