Targeting Superficial or Nodular Basal Cell Carcinoma with Topically Formulated Small Molecule Inhibitor of Smoothened

In a study from 2011, researchers investigated the effectiveness of CUR61414, a topical inhibitor of the Smoothened molecule, which is part of the Hedgehog (Hh) signaling pathway implicated in the development of basal cell carcinomas (BCC). Preclinical studies in mice showed that CUR61414 could inhibit Hh signaling in the skin, prevent hair follicle growth, and reduce BCC size. However, in a phase I clinical trial involving human patients with superficial or nodular BCCs, the topical application of CUR61414 at various concentrations (0.09%, 0.35%, 1.1%, and 3.1%) for up to 28 days did not demonstrate clinical efficacy. This discrepancy between animal models and human trials underscores the challenges in translating preclinical findings into effective human treatments.