Peer-Reviewed Publication
EMBO Mol Med2026July 30, 2026Journal Article
Inhibition of PGC1β-dependent mitochondrial biogenesis enhances EGFR-targeted therapy in lung cancer.
Zhen Chen1, Dongsheng Wang1, Songqing Fan2, Qiming Wang3,4, Yong Huang5, Pan Du5, Shidong Jia5, Suresh S Ramalingam1,6, Shi-Yong Sun7,8
1Departments of Hematology and Medical Oncology, Emory University School of Medicine Atlanta, Atlanta, GA, USA.
2Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China.
3Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
4Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China.
5Predicine, Inc, Hayward, CA, USA.
6Winship Cancer Institute of Emory University, Atlanta, GA, USA.
7Departments of Hematology and Medical Oncology, Emory University School of Medicine Atlanta, Atlanta, GA, USA. ssun@emory.edu.
8Winship Cancer Institute of Emory University, Atlanta, GA, USA. ssun@emory.edu.
Abstract
Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, show robust clinical efficacy in EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC), yet acquired resistance remains inevitable. Here, we demonstrate that osimertinib and other EGFR-TKIs suppress PPARGC1B expression and its regulated mitochondrial biogenesis in EGFRm NSCLC cells through a previously unrecogniz…
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