Progress in research of novel anticancer drugs targeting Hedgehog signaling pathway / 药学学报

ABSTRACT

The Hedgehog signaling pathway plays a key role in mammalian embryogenesis, while it is quiescent in adult tissues. The aberrant activation of Hedgehog signaling pathway has been linked to multiple types of malignant tumors, which makes it an attractive target for cancer therapy in recent years. Up to now, two Hedgehog inhibitors (vismodegib and sonidegib) have been proved by FDA for the treatment of tumors. However, drug resistance and severe adverse reactions represent the problems in their clinical application. Novel inhibitors targeting Smo, such as taladegib, NVP-LEQ506, MRT-92, and downstream or upstream of Smo receptor such as Shh ligand and Gli have been developed to overcome the drug resistance and adverse reactions. The current Hedgehog inhibitors are used for treatment of basal cell carcinoma only, while many ongoing clinical trials are conducted to investigate the antitumor effect of Hedgehog inhibitors in other malignancies. Here we reviewed the research progress of the new anticancer drugs targeting the Hedgehog signaling pathway and their prospect in variety of cancers therapy.