Cholesterol synthesis inhibitors synergize with Smoothened antagonist for treatment of Hedgehog pathway malignancies

Ref. No. 427-ZY


Aberrant activation of Hedgehog (Hh) signaling drives the formation of many malignancies including medulloblastoma (MB), basal cell carcinoma (BCC) and pancreatic cancers. Existing targeted therapies are aimed at blockade of Hh signaling through inhibition of its effector transmembrane protein Smoothened (Smo). FDA-approved Smo antagonists vismodegib and sonidegib have demonstrated efficacy in inhibiting progression of Hh-driven MB in initial clinical trials, however severe toxicity and drug resistance hampers usage of these pharmaceuticals in highly vulnerable pediatric population leaving a persistent need for safe and effective tumor treatment.


Researchers from the Fox Chase Cancer Center recently demonstrated that cholesterol synthesis is essential for function of Smo in Hh signal transduction and subsequent MB tumorigenesis. They further proved that pharmaceutical inhibition of cholesterol synthesis with statins effectively inhibit Hh signaling in cancer cells and repress tumor growth in vivo. Moreover, statins synergized with conventional Smo antagonist vismodegib in inhibiting cancer cell proliferation and tumor progression. Given the excellent safety profile, low cost and ready availability of cholesterol inhibitors, targeting cholesterol biosynthesis represents a promising strategy for the treatment of Hh-associated malignancies including BCC and pancreatic cancers.

Patent and Publication Status: Patent pending.

For Licensing/Partnering information, please contact:
Inna Khartchenko, MS, MBA
Director, Technology Transfer
E-mail: [email protected]