ArticleInternational journal of biological sciences2025
PPARG Activation of Fatty Acid Metabolism Drives Resistance to Anti-HER2 Therapies in HER2-Positive Breast Cancer.
Article in International journal of biological sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global pattern and evolution of PPARγ in breast cancer: a 25-Year bibliometric and visualized knowledge map analysis.Frontiers in oncology · 2026Pooled it
- Targeting an ASCL1-WNT11-ERK feed-forward loop to overcome pyrotinib resistance in HER2-positive breast cancer.Materials today. Bio · 2026Article
- Review
- A pan-cancer functional atlas of ADH1A reveals its conserved role in the tumor microenvironment and immunity.Translational cancer research · 2026Article
- AI-Driven Combination Therapy for Counteracting Dysregulated Genes in Lung Adenocarcinoma: Contribution-Aware Metaheuristic for Drug Repurposing.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Targeting the tripartite axis of immune-metabolic-spatial crosstalk to overcome therapy resistance in breast cancer.Frontiers in immunology · 2026Review
- Aristolochic acid I accelerates lung adenocarcinoma progression coupled with the upregulation of core oncogenic networks: an integrated network toxicology and experimental study.Frontiers in pharmacology · 2026Article
- A combined transcriptomic, epigenetic, and functional analysis identifies novel biomarkers in breast cancer.Hereditas · 2025Article
- Identification and validation of aryl hydrocarbon receptor-associated hub genes in ulcerative colitis via integrated bioinformatics analysis.Human genomics · 2025Article
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2-positive breast cancer, which accounts for approximately 15-20% of all breast cancers, is characterized by its aggressive recurrence, metastasis and reduced survival. Despite advances in anti-HER2 therapies, many patients continue to face treatment resistance, either initially or after an initial positive response, resulting in relapse or disease progression. The primary focus of this research was to identify the peroxisome proliferator-activated receptor gamma (PPARG) as a contributing factor to decreased drug sensitivity by establishing anti-HER2 drug-resistant cell lines of HER2-positive breast cancer. We found that PPARG promotes fatty acid metabolism and activates the PI3K/Akt/mTOR signaling pathway. Inhibition of fatty acid synthesis (FASN) after overexpression of PPARG, effectively blocking the activation of the PI3K/Akt/mTOR pathway and enhancing cellular anti-HER2 drug sensitivity. Co-administration of the PPARG inhibitor GW9662 has emerged as a promising strategy to augment the efficacy of anti-HER2 therapies, offering potential for clinical applications.
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