Trametinib Thwarts Activation of Survival Pathways Induced by Pro-ferroptotic Drug Conjugate ACXT-3102 Resulting in Enhanced Pancreatic Cancer Cell Death.

ABSTRACT: Ferroptosis has recently been described as an iron-dependent subroutine of programmed cell death. Cancers driven by oncogenic Ras mutations, such as pancreatic ductal adenocarcinoma, are particularly vulnerable to ferroptosis and are thus promising candidates for antineoplastic drugs targeting this unique form of programmed cell death. Our group has developed a cancer-specific drug conjugate (ACXT-3102), consisting of a proapoptotic sigma-2 ligand as a delivery moiety (SV119), linked to an inhibitor of the cystine antiporter xCT (dm-erastin), an established inducer of ferroptosis. We hypothesized that ACXT-3102 would trigger apoptosis and ferroptosis via its discrete chemical components, representing a new approach to clinical therapy for pancreatic ductal adenocarcinoma. In vitro cell via

SUBMITTER: Bishnupuri KS 

PROVIDER: S-EPMC12307273 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature