In 2010, an estimated 2.8 million cases of BCC were diagnosed in the US, and the figures have continued to climb. In fact, BCC is the most frequently occurring form of all cancers. More than one out of every three new cancers is a skin cancer, and the vast majority are BCCs.

BBC can be result in the activation of Hedgehog(HH) mutations and HH by binding with Patched (PTCH) play a role. PTCH inhabit activation of its downstream heptahelical transmembrane protein smoothened(SMO) to active the activation of Gli transcription factor. Ultimately, HH gene expressed.

In 1987, cyclopamine was proved to be inhibitor of HH signaling pathway. 13 years later, SMO was approved subsequently. Researches show that the resistance of BBC to SMO is resource from SMO mutation which also confers vismodegib resistance. What is more, mutation outside of ligand binding pocket could promote activity of SMO even without inhibitors. On the other side, mutation of binding pocket had little effect on basal SMO activity.

The activation of SMO which is downstream of HH signaling can result in any resistance of SMO-targeted inhibitor. So, the ideal therapies may contain drug combination which also targets Gli.