|Awarded On||August 16, 2017|
|Title||Capitalizing on Therapeutic Liabilities in RAS-Mutant Cancers With a Rational Combination Therapy With PARP and MEK Inhibitors|
|Award Mechanism||High Impact/High Risk|
|Institution/Organization||The University of Texas M.D. Anderson Cancer Center|
|Principal Investigator/Program Director||Anil Korkut|
|Cancer Sites||Lung and Bronchus, Pancreas, Skin|
Background Mutant RAS, one of the most common aberrations in cancer, is present in 11% of all cancers and at higher frequencies in pancreatic (90%), colorectal (50%), lung (30%), and endometrial cancers (21%) and melanoma (30%). Unfortunately, few effective therapeutic options are available for patients with mutant RAS tumors. Improved patient benefit will require development of rational approaches to identify effective combination therapies. MEK inhibitors (MEKi) target mutant RAS tumors but are ineffective as monotherapy. Poly ADP ribose polymerase inhibitors (PARPi) are effective in patients with mutations in the breast cancer 1 and 2 genes (BRCA1/2). Similarly immune-oncology “checkpoint...