Pan-KRAS inhibitors suppress proliferation through feedback regulation in pancreatic ductal adenocarcinoma.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is currently one of the most lethal cancers worldwide. Several basic studies have confirmed that Kirsten rat sarcoma virus (KRAS) is a key driver gene for the occurrence of PDAC, and KRAS mutations have also been found in most patients in clinical studies. In this study, two pan-KRAS inhibitors, BI-2852 and BAY-293, were chosen as chemical probes to investigate their antitumor potency in PDAC. Their inhibitory effects on KRAS activation were validated in vitro and their antiproliferative potency in PDAC cell lines were profiled, with half-maximal inhibitory concentration (IC₅₀) values of approximately 1 μM, demonstrating the therapeutic potential of pan-KRAS inhibitors in the treatment of PDAC. However, feedback regulation in the KRAS path

SUBMITTER: Wang CX 

PROVIDER: S-EPMC9525295 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature