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


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.

SUBMITTER: Fanelli GN 

PROVIDER: S-EPMC6990491 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The heterogeneous clinical and pathological landscapes of metastatic <i>Braf</i>-mutated colorectal cancer.

Fanelli Giuseppe Nicolò GN   Dal Pozzo Carlo Alberto CA   Depetris Ilaria I   Schirripa Marta M   Brignola Stefano S   Biason Paola P   Balistreri Mariangela M   Dal Santo Luca L   Lonardi Sara S   Munari Giada G   Loupakis Fotios F   Fassan Matteo M  

Cancer cell international 20200129


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 <i>BRAF</i> gene, a proto-oncogene involved in cell proliferation, differentiation and survival through the MAPK signaling cascade. The acquisition of <i>BRAF</i> mutation is an early event in the "serrated" CRC carcinogenetic pathway and is associated with specific and aggressive clinico-pathological a  ...[more]

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