![Improving Cancer Therapy]()
RAF proteins help regulate cell growth and survival in mammals. Since mutated RAF genes cause a large number of cancers, scientists have developed numerous RAF inhibitors with diverse structural properties. Two examples are vemurafenib and dabrafenib, which have received FDA approval to treat late-stage melanoma caused by mutant BRAF (one of the three RAF variants). But the inhibitors don’t work against cancers caused by mutations or protein amplifications that promote dimerization (a chemical structure formed from two similar subunits) of BRAF. In the August 11 online issue of Cancer Cell, Evripidis Gavathiotis, Ph.D., and colleagues show that RAF inhibitors elicit their biochemical effects via the combined outcome of two different mechanisms. The researchers provided a model of RAF inhibitor action that allows scientists to predict the biochemical effect of any RAF inhibitor based on the inhibitor’s structural properties and the particular BRAF mutation in the cell. This model should help scientists develop rationally designed RAF inhibitors and lead to more effective RAF inhibitors for treating BRAF-dependent cancers. Lead author Yang Wu, Ph.D., is a research fellow in the Gavathiotis lab. Dr. Gavathiotis is associate professor of biochemistry and of medicine.
Posted on: Tuesday, September 20, 2016