Jean Y. Tang MD PhD

Publication Details

  • Targeting Superficial or Nodular Basal Cell Carcinoma with Topically Formulated Small Molecule Inhibitor of Smoothened CLINICAL CANCER RESEARCH Tang, T., Tang, J. Y., Li, D., Reich, M., Callahan, C. A., Fu, L., Yauch, R. L., Wang, F., Kotkow, K., Chang, K. S., Shpall, E., Wu, A., Rubin, L. L., Marsters, J. C., Epstein, E. H., Caro, I., de Sauvage, F. J. 2011; 17 (10): 3378-3387

    Abstract:

    Inappropriate activation of the Hedgehog (Hh) signaling pathway in skin is critical for the development of basal cell carcinomas (BCC). We have investigated the anti-BCC efficacy of topically-applied CUR61414, an inhibitor of the Hh signal transduction molecule Smoothened.In preclinical studies, we used a depilatory model to evaluate the ability of topical formulations of CUR61414 to repress Hh responsive cells found at the base of hair follicles in normal skin. We also tested the in vivo effects of topical CUR61414 on murine BCCs developed in Ptch1 (+/-) K14-CreER2 p53 fl/fl mice. In a phase I clinical study, we evaluated the safety, tolerability, and efficacy of a multidose regimen of CUR61414 (0.09%, 0.35%, 1.1%, and 3.1%) applied topically to human superficial or nodular BCCs for up to 28 days.In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study.Our data highlight some of the challenges of translating preclinical experience into successful human results for a topical anticancer agent.

    View details for DOI 10.1158/1078-0432.CCR-10-3370

    View details for Web of Science ID 000290610000030

    View details for PubMedID 21558397

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