MGST1 facilitates novel KRAS^G12D inhibitor resistance in KRAS^G12D-mutated pancreatic ductal adenocarcinoma by inhibiting ferroptosis.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a low 5-year survival rate. Treatment options for PDAC patients are limited. Recent studies have shown promising results with MRTX1133, a KRAS^G12D inhibitor that demonstrated potent antitumor activity in various types of tumors with KRAS^G12D mutation. Resistance to KRAS inhibitors is frequently occurred and one of the main reasons for treatment failure. Understanding resistance mechanisms to novel KRAS inhibitors is crucial to ensure sustained and durable remissions.

Methods

Two KRAS^G12D inhibitor MRTX1133-resistant PDAC cell lines were established in vitro. The resistance mechanisms to KRAS^G12D inhibitor MRTX1133 against PDAC in vitro and in vivo wer

SUBMITTER: Xu C 

PROVIDER: S-EPMC11536589 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature