Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun 23:11:601722.
doi: 10.3389/fonc.2021.601722. eCollection 2021.

Current Therapeutic Strategies in BRAF-Mutant Metastatic Colorectal Cancer

Elisa Grassi  1 , Jody Corbelli  1 , Giorgio Papiani  1 , Maria Aurelia Barbera  1 , Federica Gazzaneo  1 , Stefano Tamberi  1
Affiliations
Review

Current Therapeutic Strategies in BRAF-Mutant Metastatic Colorectal Cancer

Elisa Grassi et al. Front Oncol. .

Abstract

Around 8-12% of patients with advanced colon rectal cancer (CRC) present with BRAF alterations, in particular V600E mutation, which is associated with right-side, poorly differentiated and mucinous type tumors. The presence of BRAF mutation (BRAF-mt) has been identified as a hallmark of poor prognosis and treatment optimization in this patient subgroup is an important goal. Currently, the standard of care is an aggressive strategy involving triplet chemotherapy and anti-VEGF agents, but new therapeutic approaches are emerging. Very promising results have been obtained with targeted therapy combinations, such as anti-BRAF agents plus anti-EGFR agents. Furthermore, around 60% of BRAF-mt patients show a strong association with high microsatellite instability (MSI-H) and immune checkpoint inhibitors could represent the new standard of care for this subgroup. The focus of this review is to summarize current strategies for BRAF-mt CRC treatment and highlight new therapeutic options.

Keywords: BRAF mutation; colorectal cancer; immunotherapy; microsatellites instability; targeted therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Algorithm of therapy in BRAF mt advanced colon cancer.
See this image and copyright information in PMC

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin (2018) 68(6):394–424. 10.3322/caac.21492 - DOI - PubMed
    1. Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. . The Consensus Molecular Subtypes of Colorectal Cancer. Nat Med (2015) 21(11):1350–6. 10.1038/nm.3967 - DOI - PMC - PubMed
    1. Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu–Duvaz D, Good VM, et al. . Mechanism of Activation of the RAF ERK Signaling Pathway by Oncogenic Mutations of B-RAF. Cell (2004) 116:855–67. 10.1016/S0092-8674(04)00215-6 - DOI - PubMed
    1. Ascierto PA, Kirkwood JM, Grob JJ, Simeone E, Grimaldi AM, Maio M, et al. . The Role of BRAF V600 Mutation in Melanoma. J Transl Med (2012) 10:85. 10.1186/1479-5876-10-85 - DOI - PMC - PubMed
    1. Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. . FOLFOXIRI Plus Bevacizumab Versus FOLFIRI Plus Bevacizumab as First-Line Treatment of Patients With Metastatic Colorectal Cancer: Updated Overall Survival and Molecular Subgroup Analyses of the Open-Label, Phase 3 TRIBE Study. Lancet Oncol (2015) 16:1306–15. 10.1016/S1470-2045(15)00122-9 - DOI - PubMed