Evidence map›Paper›PMID 42533181›Full record

ArticleEMBO molecular medicine2026

Inhibition of PGC1β-dependent mitochondrial biogenesis enhances EGFR-targeted therapy in lung cancer.

Zhen Chen, Dongsheng Wang, Songqing Fan, Qiming Wang, Yong Huang, Pan Du, Shidong Jia, Suresh S Ramalingam, Shi-Yong Sun

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Zhen ChenDepartments of Hematology and Medical Oncology, Emory University School of Medicine Atlanta, Atlanta, GA, USA.ORCID http://orcid.org/0000-0003-3949-5744
Dongsheng WangDepartments of Hematology and Medical Oncology, Emory University School of Medicine Atlanta, Atlanta, GA, USA.
Songqing FanDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China.
Qiming WangDepartment of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Yong HuangPredicine, Inc, Hayward, CA, USA.
Pan DuPredicine, Inc, Hayward, CA, USA.
Shidong JiaPredicine, Inc, Hayward, CA, USA.ORCID http://orcid.org/0000-0001-5854-819X
Suresh S RamalingamDepartments of Hematology and Medical Oncology, Emory University School of Medicine Atlanta, Atlanta, GA, USA.
Shi-Yong SunDepartments of Hematology and Medical Oncology, Emory University School of Medicine Atlanta, Atlanta, GA, USA. ssun@emory.edu.ORCID http://orcid.org/0000-0002-0117-8826

Funding

ECOG-ACRIN Thoracic Malignancies Integrated Translational Science CenterUG1CA233259 · NCI · EMORY UNIVERSITY · PI CARBONE, DAVID P., LEAL, TICIANA · 2019 to 2025
$5.1M
Modulation of death receptor 4 in EGFR-targeted cancer therapyR01CA223220 · NCI · EMORY UNIVERSITY · PI SUN, SHI-YONG · 2018 to 2023
$2.3M
Targeting PGC1β/PPARγ axis for overcoming acquired resistant to third generation EGFR-TKIsR01CA281148 · NCI · EMORY UNIVERSITY · PI Shi-Yong Sun · 2024 to 2026
$1.4M
David A. Cole Professorship N/AEU | Winship Cancer Institute (Winship Cancer Institute of Emory University) N/AHHS | National Institutes of Health (NIH) R01 CA223220HHS | National Institutes of Health (NIH) R01 CA281148HHS | National Institutes of Health (NIH) UG1 CA233259NCI NIH HHS R01 CA223220NCI NIH HHS R01 CA281148NCI NIH HHS UG1 CA233259
6 · The paper itself

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 unrecognized FOSL1/AP-1-mediated transactivation mechanism. Upon acquisition of osimertinib resistance, PPARGC1B expression and its encoded protein PGC1β rebound and become refractory to osimertinib-mediated suppression. Enforced overexpression of PPARGC1B confers resistance to osimertinib in sensitive EGFRm NSCLC cells, whereas PPARGC1B knockdown restores drug sensitivity in resistant cells. Moreover, combining osimertinib with the mitochondria-targeting agent CPI-613 synergistically suppresses mitochondrial biogenesis, induces apoptosis, and inhibits the growth of osimertinib-resistant cells and tumors. Collectively, these findings identify PGC1β-dependent mitochondrial biogenesis as a critical determinant of therapeutic response to osimertinib and suggest co-targeting mitochondrial metabolism as a potential strategy to overcome acquired resistance in EGFRm NSCLC.

Indexed as

Antineoplastic AgentsCarcinoma, Non-Small-Cell LungErbB ReceptorsLung NeoplasmsMitochondriaOrganelle BiogenesisProtein Kinase InhibitorsTranscription FactorsAcrylamidesAniline CompoundsAnimalsCell Line, TumorDrug Resistance, NeoplasmHumansIndolesPyrimidinesAcrylamidesAniline CompoundsAntineoplastic AgentsEGFR protein, humanErbB ReceptorsIndolesosimertinibPPARGC1B protein, humanProtein Kinase InhibitorsPyrimidinesRNA-Binding ProteinsTranscription Factors

Identifiers

PMID42533181
PMCPMC13562578

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.