RAF kinases are attractive cancer drug targets. Pre-clinical studies with cell lines and tumor xenographs bearing B-RAF(V600E) mutations indicate that RAF kinase inhibitors are effective in decreasing cell proliferation. PLX4032, which has higher affinity for B-RAF(V600E) than wild-type B-RAF, inhibits cancer progression in several animal models. The compound has demonstrated efficacy in Phase I clinical trials in the treatment of melanoma patients .
RAF kinase inhibitor treatment of cancers with wild-type or activated mutant RAS co-expressed with wild-type B-RAF may be deleterious owing to up-regulation of RAF kinase signaling. Deciphering the mechanisms of RAS-RAF-MEK-ERK signaling continues to be an important and challenging task.
