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Review
. 2020 Jan 29:20:30.
doi: 10.1186/s12935-020-1117-2. eCollection 2020.

The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer

Giuseppe Nicolò Fanelli #  1 , Carlo Alberto Dal Pozzo #  1 , Ilaria Depetris #  2 , Marta Schirripa  2 , Stefano Brignola  1 , Paola Biason  2 , Mariangela Balistreri  1 , Luca Dal Santo  1 , Sara Lonardi  2 , Giada Munari  1   2 , Fotios Loupakis #  2 , Matteo Fassan #  1
Affiliations
Review

The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer

Giuseppe Nicolò Fanelli et al. Cancer Cell Int. .

Abstract

Colorectal cancer (CRC) is a complex and molecularly heterogeneous disease representing one of the most frequent causes of cancer-related death worldwide. About 8-15% of CRCs harbor a mutation in BRAF gene, a proto-oncogene involved in cell proliferation, differentiation and survival through the MAPK signaling cascade. The acquisition of BRAF mutation is an early event in the "serrated" CRC carcinogenetic pathway and is associated with specific and aggressive clinico-pathological and molecular features. Despite that the presence of BRAF mutation is a well-recognized negative prognostic biomarker in metastatic CRC (mCRC), a great heterogeneity in survival outcome characterizes these patients, due to the complex, and still not completely fully elucidated, interactions between the clinical, genetic and epigenetic landscape of BRAF mutations. Because of the great aggressiveness of BRAF-mutated mCRCs, only 60% of patients can receive a second-line chemotherapy; so intensive combined and tailored first-line approach could be a potentially effective strategy, but to minimize the selective pressure of resistant clones and to reduce side effects, a better stratification of patients bearing BRAF mutations is needed.

Keywords: BRAF mutation; Colorectal cancer; Personalized medicine; Sequencing.

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Conflict of interest statement

Competing interestsFotios Loupakis had roles as a consultant or advisor for Roche, Bayer, Amgen and Genentech Pharmaceuticals. Sara Lonardi had roles as a consultant or advisor for Amgen, Bayer, Merck Serono and Lilly. She received research funding from Amgen and Merck Serono, and she is part of the speakers’ bureau of Lilly and BMS. Matteo Fassan had roles as a consultant or advisor for Tesaro and Astellas. He received research funding from Astellas and QED. The other authors have no competing interests to declare. The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Clinico-pathological features associated to BRAF-mutated colorectal cancers
See this image and copyright information in PMC

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