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Review
. 2023 Oct 31;15(21):5243.
doi: 10.3390/cancers15215243.

BRAF Inhibitors in Metastatic Colorectal Cancer and Mechanisms of Resistance: A Review of the Literature

Patricia Guerrero  1 , Víctor Albarrán  1 , María San Román  1 , Carlos González-Merino  1 , Coral García de Quevedo  1 , Jaime Moreno  1 , Juan Carlos Calvo  1 , Guillermo González  1 , Inmaculada Orejana  1 , Jesús Chamorro  1 , Íñigo Martínez-Delfrade  1 , Blanca Morón  1 , Belén de Frutos  1 , María Reyes Ferreiro  1
Affiliations
Review

BRAF Inhibitors in Metastatic Colorectal Cancer and Mechanisms of Resistance: A Review of the Literature

Patricia Guerrero et al. Cancers (Basel). .

Abstract

Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.

Keywords: BRAF; colorectal cancer; inhibitors; resistance.

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Conflict of interest statement

M.R.F. declares the following conflicts of interest—Advisory: Servier, Amgen, Pierre Fabre, MSD; Speaker: Servier, Amgem, Merck, Pierre Fabre; Travels and other honoraria: Sanofi, Merck, Servier, Amgen. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
MAPK and PI3K/AKT/mTOR pathway.
See this image and copyright information in PMC

References

    1. Ros J., Baraibar I., Sardo E., Mulet N., Salvà F., Argilés G., Martini G., Ciardiello D., Cuadra J.L., Tabernero J., et al. BRAF, MEK and EGFR inhibition as treatment strategies in BRAF V600E metastatic colorectal cancer. Ther. Adv. Med. Oncol. 2021;13:175883592199297. doi: 10.1177/1758835921992974. - DOI - PMC - PubMed
    1. Molina-Cerrillo J., San Román M., Pozas J., Alonso-Gordoa T., Pozas M., Conde E., Rosas M., Grande E., García-Bermejo M.L., Carrato A. BRAF Mutated Colorectal Cancer: New Treatment Approaches. Cancers. 2020;12:1571. doi: 10.3390/cancers12061571. - DOI - PMC - PubMed
    1. Rawla P., Sunkara T., Barsouk A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz. Gastroenterol. 2019;14:89–103. doi: 10.5114/pg.2018.81072. - DOI - PMC - PubMed
    1. Oddo D., Sennott E.M., Barault L., Valtorta E., Arena S., Cassingena A., Filiciotto G., Marzolla G., Elez E., Van Geel R.M.J.M., et al. Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF -Mutant Colorectal Cancer. Cancer Res. 2016;76:4504–4515. doi: 10.1158/0008-5472.CAN-16-0396. - DOI - PMC - PubMed
    1. Ciombor K.K., Strickler J.H., Bekaii-Saab T.S., Yaeger R. BRAF -Mutated Advanced Colorectal Cancer: A Rapidly Changing Therapeutic Landscape. J. Clin. Oncol. 2022;40:2706–2715. doi: 10.1200/JCO.21.02541. - DOI - PMC - PubMed