ARTICLE | Cover Story

Smoothening resistance

October 14, 2010 7:00 AM UTC

Novartis AG researchers have uncovered three possible molecular causes for brain tumor resistance to inhibitors of Smoothened, which is a key component of the Hedgehog pathway.1 The pharma has used the discovery to devise combination therapies that may bypass some cases of resistance.

Smoothened (SMO) is a G protein-coupled receptor that sends a proliferative signal in many cancers, including basal cell carcinoma (BCC) and medulloblastoma, a common pediatric brain tumor. SMO is activated by mutations in patched 1 (PTCH1) or excess production of sonic hedgehog homolog (SHH)...