INVENTION NOVELTY
Johns Hopkins researchers have developed a novel Hedgehog signaling pathway inhibitor that can be used in the treatment of various types of leukemia.
VALUE PROPOSITION
The Hedgehog (Hh) pathway has been found to be important in a number of cancers. Various Hh inhibitors, specifically Smo antagonists, are in development or have been launched for treatment of basal cell carcinoma, medulloblastoma, and multiple types of leukemia. However, there is evidence that Smo can mutate in tumors, rendering resistance to Smo inhibitors.
The disclosed invention consists of a novel Hh pathway inhibitor that acts downstream of Smo, which constitutes a novel class of Hh antagonists. This invention could be used as an alternative to or in combination with Smo inhibitors in cancer treatment plans.
TECHNICAL DETAILS
Johns Hopkins researchers have developed a novel arsenic-based Hh pathway inhibitor, arsenic trioxide (ATO). ATO acts by halting Gli2 build-up, an Hh pathway positive regulator. Tumor cell growth in medulloblastoma models is dependent on Hh and addition of ATO was found to inhibit proliferation in these models (Kim et al 2010).
STAGE OF DEVELOPMENT
There is preclinical (mouse) data demonstrating thiscompound’s anti-cancer efficacy.
ASSOCIATED PUBLICATIONS
Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector. Kim J et al, PNAS, 2010.
Issued U.S. Patent No. 7,867,492
