Award Details:
Award Type: Accelerator
Award #: A-019
Proposal Title: Allele-specific Mutant KRAS Expression Modulation as a Targeted Anti-KRAS Therapy
PI(s): Shana Kelley (NU)
Award Amount: $$100,000.00
Application Cycle: 2023
Award Start Date: January 1, 2023
Award End Date: December 31, 2023
Abstract:
KRAS substitution mutations are observed in nearly 30% of all human cancers, positioning KRAS as one of the most sought-after targets in oncology for targeted drug development, with both the current and future patient populations to be impacted numbering in millions. We deployed a proprietary immunomagnetic cell sorting platform together with functional genomics based whole-genome loss-of-function CRISPR screening for the discovery of novel mutant protein selective genetic regulators of KRAS. Through systematic functional validation of our lead hit across multiple cancer model systems as well as evaluation of anti-tumor activity, we have established the capabilities of our platform as a powerful discovery engine. Here, we will test the therapeutic potential of selective lowering of mutant KRAS protein expression as a potent anti-KRAS therapy using mutant KRAS xenograft animal models. The small-molecule based selective mutant KRAS protein expression modulator is envisioned to be a first-in-class drug candidate for targeted mutant KRAS therapy.