Novel investigational drugs for basal cell carcinoma

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Abstract

In the United States, the annual incidence of basal cell carcinoma (BCC) is close to 1 million. Ultraviolet radiation exposure is the main risk factor; however, the availability of ever more potent sunscreens and education have not prevented the rise in BCC incidence. Therefore, concerted effects to identify novel preventive and therapeutic strategies are necessary.This article summarizes our current understanding of the etiology and molecular mechanisms of BCC tumorigenesis and discusses the preclinical and clinical studies to identify agents with anti-BCC efficacy.The discovery that hyperactive Hh pathway signaling causes several cancers, including BCC, has spawned the development of many pharmacologic inhibitors of Hh signaling. Early clinical testing of the most advanced, GDC-0449, demonstrated impressive efficacy in patients with advanced BCC. Other promising anti-BCC chemopreventive strategies include drugs that are already FDA-approved for treating other diseases.Preclinical and clinical trials with pre-existing FDA-approved drugs suggest novel uses for BCC chemoprevention and treatment. Also, new chemical entities that inhibit the Hh pathway show promise, and in combination with other drugs may provide a nonsurgical cure for this most common cancer.

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