Targeting multiple kinase pathways: a change in paradigm.

Anticancer drugs that target protein kinases include small molecule inhibitors and monoclonal antibodies. Feedback loops and cross talk between signaling pathways impact significantly on the efficacy of cancer therapeutics, and resistance to targeted agents is a major barrier to effective treatments. Increasingly, therapies are being designed to target multiple kinase pathways. This can be achieved using a single agent that inhibits multiple signaling pathways or a combination of highly selective agents. In this review we discuss the principles of specifically targeting multiple kinase pathways with particular reference to angiogenic signaling pathways.