Targeting the Hedgehog signaling pathway for cancer therapy

INTRODUCTION: Hedgehog (Hh) signaling pathway plays key roles in embryonic development, formation and maintenance of cancer stem cells (CSCs) and acquisition of epithelial-to-mesenchymal transition (EMT). Since CSCs and EMT are important biological factors responsible for cancer cell invasion, metastasis, drug resistance and tumor recurrence, the Hh signaling pathway is believed to be an important target for cancer therapy. AREAS COVERED: In recent years, small-molecule inhibitors of Hh signaling have been synthesized for cancer treatment. Clinical trials using these inhibitors are being conducted to determine their toxicity profiles and efficacies. In addition, nutraceuticals (such as isoflavones, curcumin, vitamin D, etc) have been shown to inhibit cancer growth through downregulation of Hh signaling. EXPERT OPINION: Inhibition of Hh signaling is important for suppression of cancer growth, invasion, metastasis and recurrence in cancer therapy. However, targeting only one molecule in Hh signaling may not be sufficient to kill cancer cells because cancers show deregulation of multiple signals. Therefore, utilizing new technologies to determine alterations in Hh and other signals for individuals and designing combination strategies with small-molecule Hh inhibitors, nutraceuticals and other chemotherapeutics in targeted personalized therapy could have a significant effect on improving the overall survival of patients with cancers.