Inhibition of KRAS, MEK and PI3K Demonstrate Synergistic Anti-Tumor Effects in Pancreatic Ductal Adenocarcinoma Cell Lines.

ABSTRACT: Kirsten rat sarcoma virus (KRAS) mutations are widespread in pancreatic ductal adenocarcinoma (PDAC) and contribute significantly to tumor initiation, progression, tumor relapse/resistance, and prognosis of patients. Although inhibitors against KRAS mutations have been developed, this therapeutic approach is not routinely used in PDAC patients. We investigated the anti-tumor efficacy of two KRAS inhibitors BI-3406 (KRAS::SOS1 inhibitor) and sotorasib (KRAS G12C inhibitor) alone or in combination with MEK1/2 inhibitor trametinib and/or PI3K inhibitor buparlisib in seven PDAC cell lines. Whole transcriptomic analysis of combined inhibition and control groups were comparatively analyzed to explore the corresponding mechanisms of inhibitor combination. Both KRAS inhibitors and co

SUBMITTER: Ma Y 

PROVIDER: S-EPMC9497071 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature