Simvastatin overcomes the pPCK1‐pLDHA‐SPRINGlac axis‐mediated ferroptosis and chemo‐immunotherapy resistance in AKT‐hyperactivated intrahepatic cholangiocarcinoma
This study identified the pAKT-pPCK1-pLDHA-SPRINGlac axis as a novel mechanism driving ferroptosis resistance in AKT-hyperactivated ICC by associating glycolytic activation with MVA flux reprogramming. Targeting this axis, potentially through statin-based therapies, may offer a strategy to sensitize ICC cells to ferroptosis and improve treatment outcomes.
Authors
- Yunhui Fan (ORCID: https://orcid.org/0000-0001-7350-9084)
- Wanguang Zhang (ORCID: https://orcid.org/0000-0003-3184-9907)
- Guangzhen Cai (ORCID: https://orcid.org/0000-0003-2575-555X)
- Jinghan Zhu (ORCID: https://orcid.org/0000-0002-6310-1672)
- Yang Wu (ORCID: https://orcid.org/0000-0002-0906-9667)
- Yixiao Xiong (ORCID: https://orcid.org/0000-0003-1573-4974)
- Yuanxiang Lu (ORCID: https://orcid.org/0009-0004-2948-4931)
- Zeyang Ding (ORCID: https://orcid.org/0000-0001-5826-0970)
- Yuxin Zhang (ORCID: https://orcid.org/0000-0002-5144-0693)
- Xiaoping Chen (ORCID: https://orcid.org/0009-0002-3306-2913)
- Huifang Liang (ORCID: https://orcid.org/0000-0001-6874-3634)
- Hong Zhu
- Kun Cheng (ORCID: https://orcid.org/0000-0003-0742-1978)
Institutions
- Academy of Medical Sciences (GB)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- National Health and Family Planning Commission (CN)
- Soochow University (CN)
- Saudi Center for Organ Transplantation (SA)
- First Affiliated Hospital of Soochow University (CN)
- Tongji Hospital (CN)
- Pancreas Centre (Canada) (CA)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Cancer Communications
- Published
- 2025-05-29
- DOI
- https://doi.org/10.1002/cac2.70036
- Citations
- 11
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 16.70
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation