KRAS is the most commonly mutated gene in cancer, but targeting the mutant protein is notoriously difficult because current therapies work only for certain KRAS mutations. This led researchers Kathleen McAndrews, Ph.D., Anirban Maitra, M.B.B.S., Raghu Kalluri, M.D., Ph.D., and Timothy Heffernan, Ph.D., to examine the efficacy of a first-in-class inhibitor called BI-2493. This pan-KRAS inhibitor can target the mutant protein in multiple cancer types, regardless of the specific mutation present. BI-2493 was developed as part of the strategic collaboration between Boehringer Ingelheim and MD Anderson. In several models of pancreatic cancer, BI-2493 effectively suppressed tumor growth in vitro and prolonged survival in vivo, with further analysis showing confirmed RAS pathway inhibition. BI-2493 also remodeled the tumor microenvironment of immune-compromised models, increasing intratumoral immune cells and decreasing myeloid cells, allowing for better immunotherapy response. These findings highlight the therapeutic potential of combining BI-2493 with other treatments to inhibit a variety of KRAS mutations and improve patient outcomes.
First-in-class pan-KRAS inhibitor shows strong antitumor activity in preclinical models
