Angiogenesis inhibition is now a clinically validated approach to cancer therapy. For the skin, two topical agents with antiangiogenic and anti-tumor properties, diclofenac and imiquimod, have shown excellent results for treating AK and BCC. For imiquimod, dosing this agent for an antiangiogenic response is effective and well tolerated for treating non-melanoma skin cancers.

Looking ahead, there is considerable interest in angiogenesis inhibitors, either topical or systemic, for skin cancer prevention in people predisposed to the disease, such as organ transplant recipients or in individuals with extensive sun damage. One agent, sirolimus (rapamycin, Rapamune), a macrolide antiabiotic and immunosuppressant, was accidentally found to decrease the incidence of skin tumors in organ transplant patients. A number of studies have now documented remission of non-melanoma skin cancers and Kaposi’s sarcoma in kidney transplant patients treated with sirolimus.¹² Other antiangiogenic substances that show potential for the treatment of non-melanoma skin cancer include perillyl alcohol and solenopsin, a component of venom of the fire ant. Perillyl alcohol (POH), found in the essential oils of several plants (lavender, mints, cherries) has proven antiangiogenic and antitumor properties.¹³ Solenopsin, the primary alkaloid from the fire ant Solenopsis invicta, inhibits a key regulator of angiogenesis and other cellular functions involved in skin cancer development.¹⁴ These novel compounds, in addition to established antiangiogenic agents, “off-the-shelf” drugs, and dietary substances with antiangiogenic properties, show great promise as skin cancer therapy.