Hedgehog Signaling and Cancer Treatment Resistance

Cancer treatment modalities, including radiotherapy (RT), chemotherapy, and chemoradiotherapy (CRT) are considered effective for many types of cancers through their cytotoxic effects, including DNA damage. However, the development of resistance to these cancer treatment modalities remains a limitation to be overcome. Growing evidence from preclinical and translational research suggests that hedgehog (HH) signaling, one of cancer stem cell (CSC) signaling pathways, may affect the treatment outcome of cancer. This chapter briefly introduces the correlation between CSC and treatment resistance. The possible role of HH signaling in cancer treatment resistance is addressed from four aspects, including the induction of tumor regrowth and CSCs, anti-apoptosis and cell cycle regulation, modulation of DNA damage repair, and stimulation of multiple drug resistant transporter system. It concludes that HH signaling pathway could be regarded a target for the development of novel therapeutics against cancer as well as CSCs. Several pharmacological agents with HH blockade activity are currently undergoing clinical investigations.