University Of Pennsylvania Study Shows Promise Of New Anti-KRAS Drug For Pancreatic Cancer

Asmall molecule inhibitor that attacks the difficult to target, cancer-causing gene mutation KRAS, found in nearly 30% of all human tumors, successfully shrunk tumors or stopped cancer growth in preclinical models of pancreatic cancer, researchers from Penn Medicine’s Abramson Cancer Center find, suggesting the drug is a strong candidate for clinical trials. The study is published in Cancer Discovery.

“The results of this study are in stark contrast to anything we’ve seen before in pancreatic cancer,” says co-corresponding senior author Ben Stanger, the Hanna Wise Professor in Cancer Research in the Perelman School of Medicine at the University of Pennsylvania and director of the Penn Pancreatic Cancer Research Center. “Even in preclinical research models for this cancer type, most drugs tested within the last decade—including novel immunotherapies—have had limited impact.”

Patients with pancreatic cancer have an overall poor prognosis with a five-year survival rate of 11% and limited treatment options. Nearly 90% of pancreatic cancers are driven by a mutation in the KRAS gene, the most common oncogene across cancer types. The first targeted therapy for KRAS was approved last year for non-small cell lung cancer with KRAS G12C mutations, but only 2% of pancreatic cancers express that type of mutation.

The small molecule inhibitor MRTX1133 specifically targets KRAS G12D. The Penn study shows the KRAS-inhibitor not only directly targets cancer cells, but also unexpectedly cooperates with the immune system to produce a durable response to treatment, which is important because cancer eventually finds a way to evade most targeted therapies.