Overview

Increasing functional p53 has the potential to treat aggressive cancers with dysfunctional wild-type p53 that represent about 50% of all human tumors. These cancers, such as colorectal (KRAS wild-type), esophageal, triple-negative breast, glioblastoma, and pancreatic, have limited treatment options and poor patient survival rates.

For nearly forty years, drug hunters have believed that drugs that reactivate functional p53's natural tumor suppressing ability would hold powerful anti-cancer activity. Several pharmaceutical and biotech companies have unsuccessfully attempted to drug wild-type p53 through pursuing small-molecule inhibitors of MDM2, an oncoprotein that directly binds and inactivates p53 function. However, developmental MDM2 drug inhibitors trigger a feedback loop causing MDM2 expression to skyrocket, further suppressing p53 levels.

PARN inhibition is a novel, first-in-class therapeutics strategy that gets around the MDM2 drug inhibitor feedback loop to drug p53 and restore functional p53 to treat wild-type p53 cancers. PARN inhibition has the potential to treat 50% of all human tumors.