The hedgehog pathway inhibitor GDC-0449 shows potential in skin and other cancers

Background: The hedgehog signalling pathway is vital in early development, but then becomes dormant, except in some cancer tumours. Hedgehog inhibitors are being developed for potential use in cancer. Objectives/methods: The objective of this evaluation is to review the initial clinical studies of the hedgehog inhibitor, GDC-0449, in subjects with cancer. Results: Phase I trials have shown that GDC-0449 has benefits in subjects with metastatic or locally advanced basal-cell carcinoma and in one subject with medulloblastoma. GDC-0449 was well tolerated. Conclusions: Long-term efficacy and safety studies of GDC-0449 in these conditions and other solid cancers are now underway. These clinical trials with GDC-0449, and trials with other hedgehog inhibitors, will reveal whether it is beneficial and safe to inhibit the hedgehog pathway in a wide range of solid tumours or not.