Targeting the serrated pathway of colorectal cancer with mutation in BRAF

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.

Work in the authors' laboratory was supported by Fundação para a Ciência e Tecnologia (FCT) [through centre grant UID/MULTI/04046/2013 to BioISI, contract ‘FCT Investigator’ to PM, and fellowship SFRH/ BPD/63395/2009 to VG] and by the Portuguese association Maratona da Saúde — Cancro 2014 to PJ.