DDR1 sustains ferroptosis resistance in pancreatic ductal adenocarcinoma via SLC40A1-mediated iron homeostasis.

ACSL5 drives pancreatic ductal adenocarcinoma by suppressing mitophagy and enhancing ferroptosis resistance via the JAK1-STAT1-OASL axis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited therapeutic options. Here, we identify long-chain acyl-CoA synthetase 5 (ACSL5) as a key oncogenic driver and prognostic biomarker in PDAC. Combined transcriptomic analysis of 51 PDAC samples and three public databases (GSE183795, GSE287...

Ferroptosis in Pancreatic Ductal Adenocarcinoma: Mechanisms, Tumor Biology, and Therapeutic Opportunities.

This Review synthesizes current understanding of the core molecular mechanisms governing ferroptosis, including dysregulated iron metabolism, lipid peroxidation pathways, and failure of antioxidant defense systems, and reviews the rapidly expanding spectrum of ferroptosis-based therapeutic strategies.

4-aminoquinolines promote redox-dependent ferroptosis sensitization in pancreatic ductal adenocarcinoma cells

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer marked by oxidative stress, metabolic rewiring, and resistance to cell death. Ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, represents a promising therapeutic vulnerability in PDAC; however, intrinsic resistance to...

IRE1α-XBP1s signaling links lipid homeostasis to hypoxic maladaptation and KRAS inhibitor responses in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is among the most hypoxic human tumors. Because fatty acid (FA) desaturation is oxygen-dependent, hypoxia can limit monounsaturated FA (MUFA) production, increase membrane lipid saturation, and activate endoplasmic reticulum stress responses, including IRE1α-XBP1s. Here, we found...

MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.

KLF5-driven G6PD protects lung squamous cell carcinoma from ferroptosis by sustaining mitochondrial homeostasis and SLC7A11-dependent cystine uptake.

AIMS Lung squamous cell carcinoma (LUSC) is a highly aggressive malignancy with limited therapeutic options. Ferroptosis has emerged as a promising antitumor strategy. However, the metabolic determinants governing ferroptotic vulnerability in LUSC remain incompletely understood. We investigated glucose-6-phosphate dehy...