2. Academic Validation
  3. Utidelone suppresses PDAC growth and enhances gemcitabine therapy by inducing immunogenic cell death

Utidelone suppresses PDAC growth and enhances gemcitabine therapy by inducing immunogenic cell death

  • iScience. 2025 Apr 23;28(6):112509. doi: 10.1016/j.isci.2025.112509.
Jingyi Zhou 1 2,  Kangnan Zhang 3 4,  Chuan Liu 1,  Jiang Long 5,  Haitao Gu 5,  Hanguang Dong 5,  Chuntao Wu 5,  Ling Xu 3,  Fan Wang 1 2,  Qi Li 1 2
Affiliations

Affiliations

  • 1 Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • 2 Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • 3 Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.
  • 4 Clinical Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
PMID: 40530421 DOI: 10.1016/j.isci.2025.112509
Abstract

Utidelone (UTD1), a microtubule-stabilizing agent, shows antitumor effects in solid tumors but its role in pancreatic ductal adenocarcinoma (PDAC) is unclear. We assessed UTD1 alone and with gemcitabine (GEM) using in vitro assays (CCK8, colony formation, Apoptosis, and cell cycle) and in vivo xenograft and immunocompetent KPC models. UTD1 suppressed cell proliferation, induced Apoptosis, and caused G2/M arrest dose-dependently. The UTD1+GEM combination enhanced antitumor efficacy in vitro and in vivo. Mechanistically, UTD1 + GEM increased immunogenic cell death (ICD) markers. In KPC models, the combination improved survival, reduced tumors, and increased CD4+/CD8+ T cell infiltration and PD-L1 expression. Clinically, UTD1 + GEM demonstrated good tolerability, high disease control rates, and favorable immunophenotypic changes. These findings suggest UTD1 triggers ICD, enhancing immune recognition of tumor cells, and highlight its potential as a therapeutic strategy for PDAC.

Keywords

Cancer; Cell biology; Molecular biology.

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