ASIC3–PLCG1 axis–driven macropinocytosis promotes osimertinib drug-tolerant persistence in malignant pleural effusion–associated NSCLC
ASIC3 is a central regulator of acidosis-driven drug persistence in MPE-associated NSCLC, sustaining osimertinib tolerance through PLCG1-dependent macropinocytosis and metabolic reprogramming. Targeting ASIC3 restores TKI sensitivity by disrupting nutrient acquisition, autophagy, and metabolic adaptation, representing a promising therapeutic strategy to prevent or delay EGFR-TKI resistance.
Authors
- Chih‐Ying Changchien
- Wen‐Chien Huang (ORCID: https://orcid.org/0000-0002-9482-8188)
- Chieh-Yung Wang
- Chen‐Liang Tsai (ORCID: https://orcid.org/0000-0001-9783-5423)
- Chih‐Feng Chian (ORCID: https://orcid.org/0000-0001-8282-2056)
- Ying Chen (ORCID: https://orcid.org/0000-0001-6303-5858)
- Yi‐Hsuan Lin (ORCID: https://orcid.org/0000-0003-4158-7154)
Institutions
- Mackay Memorial Hospital (TW)
- National Defense Medical College (JP)
- National Defense Medical Center (TW)
Publication Details
- Journal
- European Journal of Pharmaceutical Sciences
- Published
- 2025-12-17
- DOI
- https://doi.org/10.1016/j.ejps.2025.107417
- Primary Topic
- Lung Cancer Treatments and Mutations
- Type
- article
- Field-Weighted Citation Impact
- 0.00