Targeting Mutant BRAF in Colorectal Cancer

BackgroundMutations in BRAF V600E oncogene (BRAFMT) occurs in 8-15% of colorectal cancer (CRC) patients1.This mutation constitutively activates MAPK signalling, resulting in a proliferative and survival advantage for the tumour cells and oncogenic BRAF status has been linked with poor prognosis2.Despite introduction of the BRAFMT specific inhibitor Vemurafenib in metastatic melanoma3, there is no effective treatment strategy for BRAFMT CRC patients.This study aimed to assess the effectiveness of Ganetespib (HSP90 inhibitor), the multi-kinase inhibitor (CRAF/ VEGFR/PDGFR) Sorafenib and the BRAFMT inhibitor Vemurafenib in BRAFMT CRC cell line models. MethodsBRAF MT RKO F6-8 (MT/WT) and isogenic wild-type T29 (null/WT) cell lines were used.MTT assays were used to determine IC50 values.Protein expression was determined by Western Blotting.Levels of apoptotic cells were assessed by flow cytometry.