New uses for old drugs: Identification of Hedgehog pathway antagonists previously tested in humans

Hedgehog (Hh) pathway activity is responsible for the growth of lethal cancers such as small cell lung cancer, and carcinomas of the esophagus, stomach, pancreas, biliary tract, and prostate, and account for as many as 25% of cancer deaths. Evidence for the critical role of continuous Hh pathway activity comes from the ability of cyclopamine, a potent antagonist of the Hh signaling pathway, to block growth in mouse models of these cancer types. Scientists at JHU have now identified a pathway antagonist, an FDA drug approved for another indication, whose reported serum levels in humans are >10-fold the IC50 in pathway inhibition. This FDA-approved drug is as effective as cyclopamine in suppressing prostate cancer metastasis and growth of human metastatic prostate cancer xenografts in mouse models. Description (Set) Proposed Use (Set) Several biotech and pharmaceutical companies have mounted significant efforts to develop cyclopamine or other small molecules capable of Hh pathway blockade as a strategy for novel, non-toxic cancer treatments. Despite the massive scale of the resources dedicated to this approach, several years of further development likely will be required before safety and efficacy of drug candidates can be tested in human patients. In comparison, by utilizing drugs that are already FDA approved, this invention can rapidly bridge the gap between the lab and clinic in the treatment of cancer.

Inventor(s): Beachy, Philip A.

Type of Offer: Licensing

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