| Abstract: |
The hunt for mutated and activated kinases in cancer has proceeded at an accelerated pace since the successful treatment of chronic myelogenous leukemia with imatinib and with the development of new genomic sequencing technologies. The identification of activating mutations in B-Raf in a major subset of melanomas was first reported in 2002. Basic laboratory experiments confirmed the ability of mutant B-Raf to function as a driver oncogene in vivo. Relatively rapidly, inhibitors that preferentially target the mutated kinase were developed and tested clinically, and these studies revealed that the majority of patients bearing V600E B-Raf mutant melanomas showed a clinical response. Positive results of a randomized phase III clinical trial were released in early 2011. The current phase of this remarkable story is focused upon understanding mechanisms of primary and secondary resistance to B-Raf inhibitors in the clinic. © Springer Science+Business Media, LLC 2012. All rights reserved. |
