Abstract
Background Mutations 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.
Highlights
Mutations in BRAF V600E oncogene (BRAFMT) occurs in 8-15% of colorectal cancer (CRC) patients[1]
The RKO BRAFMT cell line was sensitive to Sorafenib and Ganetespib compared to the isogenic BRAFWT clone (IC50 1.4μM vs. 0.9 μM and 0.86 nM vs. 0.79nM respectively)
Western blotting showed that neither Sorafenib nor Ganetespib had an observable effect in targeting mutant BRAF
Summary
Mutations in BRAF V600E oncogene (BRAFMT) occurs in 8-15% of colorectal cancer (CRC) patients[1]. 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 prognosis[2]. Despite introduction of the BRAFMT specific inhibitor Vemurafenib in metastatic melanoma[3], 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
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