Bringing on the BRAF

The BRAF inhibitor Zelboraf vemurafenib from Daiichi Sankyo Co. Ltd. and Roche produces about an 80% response rate in its approved indication of BRAF-mutant melanoma but only about a 5% rate in colorectal tumors with the same mutation. Now, European and U.S. teams have independently pinpointed epidermal growth factor receptor as the likely missing link in these colorectal cancers, suggesting treatments combining inhibitors of both targets could be more effective than monotherapy.^1,2 Both groups are independently planning clinical trials with such combinations.

A group led by René Bernards, professor and head of molecular carcinogenesis at The Netherlands Cancer Institute, used an RNAi-based genetic screen in human mutant colorectal cancer cells to identify kinases whose knockdown synergized with inhibition of the V600E mutant form of BRAF...