Trametinib Thwarts Activation of Survival Pathways Induced by Pro-ferroptotic Drug Conjugate ACXT-3102 Resulting in Enhanced Pancreatic Cancer Cell Death. (PubMed, Mol Cancer Ther) - Jul 18, 2025 - "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 suspected that this was a compensatory reaction and that ACXT-3102-induced cancer cell death would be augmented by inhibition of MAPK/ERK signaling. We successfully combined ACXT-3102 with trametinib (MEK inhibitor) to enhance the overall efficacy of treatment in vitro and in vivo, presumably by targeting ACXT-3102-induced upregulation of MAPK/ERK."
Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • CASP7 • DUSP6 • GPX4
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Brian A Van Tine; Dirk Spitzer; Kenneth F Newcomer; Kumar S Bishnupuri; Lauren Ross; Li Ye; Qingqing Gong; Rony Takchi; Suwanna Vangveravong; William G Hawkins
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