Skip to main page content
U.S. flag
See More

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
. 2020 Jun 14;12(6):1571.
doi: 10.3390/cancers12061571.

BRAF Mutated Colorectal Cancer: New Treatment Approaches

Javier Molina-Cerrillo  1   2   3 , María San Román  1 , Javier Pozas  1 , Teresa Alonso-Gordoa  1   2   3 , Miguel Pozas  1 , Elisa Conde  4 , Marta Rosas  5 , Enrique Grande  6 , María Laura García-Bermejo  4 , Alfredo Carrato  1   2   3
Affiliations
Review

BRAF Mutated Colorectal Cancer: New Treatment Approaches

Javier Molina-Cerrillo et al. Cancers (Basel). .

Abstract

Colon cancer is one of the most frequently diagnosed malignancies in adults, considering both its incidence and prevalence. Anatomically, the right colon is considered as being from the cecum to the splenic flexure, and the left colon is from the splenic flexure to the rectum. Sidedness is a surrogate of a wide spectrum of colorectal cancer (CRC) biology features (embryology, microbiome, methylation, microsatellite instability (MSI), BRAF, aging, KRAS, consensus molecular subtypes (CMS), etc.), which result in prognostic factors. Different molecular subtypes have been identified, according to genomic and transcriptomic criteria. A subgroup harboring a BRAF mutation has been described, and represents approximately 10% of the patients diagnosed with colon cancer. This subgroup has morphological, clinical, and therapeutic characteristics that differ substantially from patients who do not carry this genetic alteration. Unfortunately, there is no established standard of care for this particular cohort of patients. This manuscript aims to study the biology of this subgroup of colon cancer, to understand the current approach in clinical research.

Keywords: BRAF; CXCR4; colorectal cancer; immunotherapy; tyrosine kinases.

PubMed Disclaimer

Conflict of interest statement

Teresa Alonso-Gordoa: Pfizer, Ipsen, Bristol-Myers Squibb, Roche, Eusa Pharma, MerckSharp&Dohme (C/A, SAB), Roche (RF). Enrique Grande: Pfizer, Bristol-Myers Squibb, Ipsen, Roche, Eisai, Eusa Pharma, MerckSharp&Dohme, Sanofi-Genzyme, Adacap, Novartis, PierreFabre, Lexicon, Celgene (C/A, SAB), Pfizer, AstraZeneca, MTEM/Threshold, Roche, Ipsen, Lexicon (RF). The rest of authors declares no conflict of interest. (C/A): Consulting/Advisory relationship; (RF) Research Funding; (SAB) Scientific Advisory Board.

Figures

Figure 1
Figure 1
EGFR (epidermal growth factor receptor) and VEGFR (vascular endothelial growth factor receptor) signalization pathways. BRAF plays a central role in this key pathway in colorectal cancer. In the legend is represented the different targeted therapeutic and drugs strategies developed in this setting of patients.
Figure 2
Figure 2
Chemokine (C-X-C motif) receptor 4 (CXCR4)/EGFR pathways crosstalk. CXCR4 is able to upregulate EGFR activation and finally ERK phosphorylation.
See this image and copyright information in PMC

References

    1. Rawla P., Sunkara T., Barsouk A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Przeglad Gastroenterol. 2019;14:89–103. doi: 10.5114/pg.2018.81072. - DOI - PMC - PubMed
    1. Gómez-España M.A., Gallego J., González-Flores E., Maurel J., Páez D., Sastre J., Aparicio J., Benavides M., Feliu J., Vera R. SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018) Clin. Transl. Oncol. 2019;21:46–54. doi: 10.1007/s12094-018-02002-w. - DOI - PMC - PubMed
    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Linevsky J.K. In: Management of Gastrointestinal Diseases. Winawer S.J., editor. Gower Medical Publishing; New York, NY, USA: 1992. p. 1050.
    1. Carini F., Mazzola M., Rappa F., Jurjus A., Geagea A.G., Al Kattar S., Bou-Assi T., Jurjus R., Damiani P., Leone A., et al. Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants. Anticancer Res. 2017;37:4759–4766. - PubMed