Antiangiogenesis in the treatment of skin cancer.

Angiogenesis is the formation of new capillary blood vessels from existing vasculature. Cancers are dependent upon angiogenesis for their growth. Inhibition of angiogenesis can slow, halt, or regress tumors. Angiogenesis inhibition is now validated for the treatment of cancer using a variety of approved biologic, small molecule, multitargeting, and immunomodulatory agents. In the skin, strategies to inhibit angiogenesis-signaling pathways include blockade of COX-2, m-TOR, sonic hedgehog, growth factor receptor activation, and activation of Toll-like receptors (TLR). The agent with the most clinical experience as a topical antiangiogenic therapy is imiquimod. Imiquimod is a TLR agonist, with immune response modifying properties that also stimulates antiangiogenic cytokines, downregulates the expression of proangiogenic factors, upregulates the expression of endogenous inhibitors, and induces endothelial cell apoptosis. By titrating its dosing for angiogenesis inhibitory activity and not for gross inflammation, imiquimod can be applied in an efficacious and well-tolerated fashion to treat skin cancer.