Characterization of mechanism of action behind acquired resistance to KRASG12D Inhibition in Pancreatic Ductal Adenocarcinoma

This statistic underscores the critical need for innovative and effective therapeutic approaches. Recent therapeutic efforts have centered on targeting KRAS mutations directly, with particular focus on the development of specific inhibitors.

MRTX1133, seletive non-covalent inhibitor, has shown significant preclinical efficacy in targeting the KRASG12D mutation, the most prevalent KRAS variant in PDAC. However, the emergence of resistance to targeted therapies poses a substantial barrier to achieving sustained clinical benefit. This study aims to delineate the molecular and cellular mechanisms underlying resistance to MRTX1133 in preclinical PDAC models.