IRE1α-XBP1s signaling links lipid homeostasis to hypoxic maladaptation and KRAS inhibitor responses in pancreatic ductal adenocarcinoma. (PubMed, Proc Natl Acad Sci U S A) - Sep 23, 2026 - "Importantly, the IRE1α RNase inhibitor B-I09 clearly synergized with MRTX1133 in vitro and in vivo, moreover, this is likely due to MYC-fatty acid synthase (FASN) dysregulation. Together, these findings identify context-dependent vulnerabilities of the IRE1α-XBP1s pathway in PDAC and provide a rationale for combining inhibition of IRE1α and KRAS to enhance therapeutic responses."
Journal • Metabolic Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • FASN • KRAS • XBP1
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Brian Keith; Carson D Poltorack; Cassidy Pagen; Chih-Chi Andrew Hu; Chih-Hang Anthony Tang; Gusangyu Yin; Justin M Berg; Laura C Kim; M Celeste Simon; Mai Wang; Morgan Brown; Nathan J Coffey; Xu Han; Xuanyan Cai; Yanqing Jiang; Yihui Shen; Yizheng Xue; Zian Zhang
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