Pan-KRAS Inhibitors BI-2493 and BI-2865 Display Potent Antitumor Activity in Tumors with KRAS Wild-type Allele Amplification.

ABSTRACT: KRASG12C selective inhibitors, such as sotorasib and adagrasib, have raised hopes of targeting other KRAS-mutant alleles in patients with cancer. We report that KRAS wild-type (WT)-amplified tumor models are sensitive to treatment with the small-molecule KRAS inhibitors BI-2493 and BI-2865. These pan-KRAS inhibitors directly target the "OFF" state of KRAS and result in potent antitumor activity in preclinical models of cancers driven by KRAS-mutant proteins. In this study, we used the high-throughput cellular viability Profiling Relative Inhibition Simultaneously in Mixtures assay to assess the antiproliferative activity of BI-2493 in a 900+ cancer cell line panel, expanding on our previous work. KRAS WT-amplified cancer cell lines, with a copy number >7, were identified as the most sensit

SUBMITTER: Tedeschi A 

PROVIDER: S-EPMC11962398 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature