Elesclomol-copper combination synergistically targets mitochondrial metabolism in cancer stem cells to overcome chemoresistance in PDAC.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis, partly due to cancer stem cells (CSCs) that drive progression and treatment resistance. We explored the therapeutic potential of inducing cuproptosis, a copper-dependent, regulated cell death, in CSC-enriched PDAC models. Using human and murine PDAC models, we evaluated elesclomol, a copper transport enhancer. Elesclomol alone had minimal effects; combined with copper chloride (CuCl₂), it significantly and irreversibly reduced CSC phenotypes without affecting non-transformed cells. Mechanistically, only the combination raised intracellular copper ions 2- to 4-fold, decreased iron-sulfur cluster proteins, and caused lipoylated dihydrolipoamide S-acetyltransferase (DLAT) accumulation in mitochon

SUBMITTER: Yu Q 

PROVIDER: S-EPMC12703165 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature