Targeting the serrated pathway of colorectal cancer with mutation in BRAF

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Targeting the serrated pathway of colorectal cancer with mutation in BRAF

Thursday, 04.08.2016

Paulo Matos (1-3), Vânia Gonçalves (2,3), Peter Jordan (2,3)

1. Department of Chemistry and Biochemistry, Faculty of Sciences, University of Lisbon, Portugal

2. BioISI — Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Portugal

3. Department of Human Genetics, National Health Institute ‘Dr. Ricardo Jorge’, Lisbon, Portugal

A recently acknowledged morphological pathway to colorectal cancer originates from precursor polyps with a serrated appearance due to branching and folding of the colon epithelium. This serrated origin accounts for up to 30% of all colorectal tumors but these are heterogeneous regarding molecular characteristics and patient outcome. Here we review the current knowledge about the classification of this tumor subtype and its association with five key features: mutation status of the BRAF or KRAS genes, the CpG island methylation phenotype, microsatellite instability, immune cell infiltration, and overexpression of GTPase RAC1b. Subsequently, available therapeutic approaches for targeting these molecular characteristics are presented and critically discussed.

Journal: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

http://www.sciencedirect.com/science/article/pii/S0304419X16300439