Mitochondrial fatty acid oxidation as the target for blocking therapyresistance and inhibiting tumor recurrence: The proof-of-principle model demonstrated for ovarian cancer cells

Sep 29, 2026

Cancer patients treated with current chemotherapeutic and targeted therapies often achieve partial remission but later relapse with more aggressive, drug-resistant tumor phenotypes. Drug-tolerant persister (DTP) cells contribute to residual tumors after systemic anticancer treatment and drive acquired drug resistance. Novel approaches that specifically target DTP cells are urgently needed to prevent therapy resistance and subsequent tumor recurrence, particularly in ovarian cancer.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

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Highlights

Paclitaxel induced persister cells show low proliferation and tolerance

Paclitaxel-tolerant persister cells show increased mitochondrial FAO

Combination therapy with paclitaxel and FAO inhibitor ST1326 prevents relapse

CEBPB/HADHA-dependent FAO as a therapeutic target in persister cells

Article information

Keywords

Abstract

Journal of Advanced Research 79 (2026) 571–585 Contents lists available at ScienceDirect Journal of Advanced Research journal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare) Mitochondrial fatty acid oxidation as the target for blocking therapyresistance and inhibiting tumor recurrence: The proof-of-principle model demonstrated for ovarian cancer cells Hui Lin a,b, 1, Lingfang Wang a, 1, Hanwen Chend, 1, Yuqing Shen e, 1, Conghui Wang a,c, Yite Xuef, Zhi Zheng Yanan Zhang h, Dajing Xia a,i, Yihua Wu a,i, Fenfen Wang a,c, Xiao Li a,c, Xiaodong Cheng a,c, Hui Wang a,c,j, Junfen Xu a,c,⁎, Weiguo Lu a,b,c,⁎⁎ a Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006 Zhejiang, China b Zhejiang Key Laboratory of Maternal and Infant Health, Hangzhou 310006 Zhejiang, China c Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou 310006 Zhejiang, China d Department of Gastroenterology, the Second Afﬁliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009 Zhejiang, China e Department of Endocrinology, the First Afﬁliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003 Zhejiang, China f Department of Gynecological Oncology, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou 310022 Zhejiang, China g Department of Obstetrics and Gynecology, Wenzhou People’s Hospital, Wenzhou 325000 Zhejiang, China h Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing 100044, China i Department of Toxicology, Zhejiang University School of Public Health, Hangzhou 310058 Zhejiang, China j Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Hangzhou 310006 Zhejiang, China g , h i g h l i g h t s • Paclitaxel induced transient ovarian cancer persister cells characterized by low proliferation and paclitaxel tolerance • Paclitaxel-tolerant ovarian cancer persister cells exhibited increased mitochondrial FAO • Combination therapy with paclitaxeland FAO inhibitor ST1326 prevented ovarian tumor relapse with satisfactory biosafety • CEBPB/HADHA-dependent FAO was a potential therapeutic target in persister cells g r a p h i c a l a b s t r a c t Abbreviations: ActD, Actinomycin D; AML, acute myeloid leukemia; ANOVA, one-way analysis of variance; ATCC, American Type Culture Collection; ATP, adenosine triphosphate; BCAA, branched chain amino acid; BCAT1, branched-chain amino acid aminotransferase 1; BME, basement membrane extract; CCK-8, cell counting kit-8; cDNA, complementary DNA; CEBPB, CCAAT enhancer binding protein beta; CFSE, carboxyﬂuorescein diacetate succinimidyl ester; ChIP, chromatin immunoprecipitation; CST, Cell Signaling Technology; ddH2O, double distilled H2O; DIA, data independent acquisition; DMSO, dimethyl sulfoxide; DTP, drug-tolerant persister; EMT, epithelial– mesenchymal transition; ER, endoplasmic reticulum; FAO, fatty acid oxidation; FFA, free fatty acid; FIGO, International Federation of Gynecology and Obstetrics; FITC,ﬂuorescein isothiocyanate; GO, Gene Ontology; GSEA, Gene Set Enrichment Analysis; HADHA, hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; HE, hematoxylin-eosin; HGSOC, high-grade serous ovarian carcinoma; IC50, half maximal inhibitory concentration; IHC, immunohistochemistry; KEGG, Kyoto Encyclopedia of Genes and Genomes; mtROS, mitochondrial ROS; NAC, neoadjuvant chemotherapy; NADP, nicotinamide adenine dinucleotide phosphate; NC, negative control; NOD/SCID, nonobese diabetic/severe-combined immunodeﬁcient; OCR, oxygen consumption rate; OS, overall survival; OXPHOS, oxidative phosphorylation; PCA, principal component analysis; PDO, patient-derived organoid; PFA, paraformaldehyde; PFI, progression-free interval; PFS, progression-free survival; PI, propidium iodide; PRIDE, Proteomics I

FAQs

Why are drug-tolerant persister (DTP) cells important in cancer relapse?

DTP cells help explain residual tumors after systemic anticancer therapy and contribute to the emergence of acquired drug resistance, leading to relapse with more aggressive phenotypes.

What therapeutic strategy does the study focus on for ovarian cancer?

The work targets mitochondrial fatty acid oxidation (FAO) in DTP cells, evaluating whether blocking FAO can suppress therapy resistance and inhibit tumor recurrence.

What does the study highlight about paclitaxel and persister cells?

Paclitaxel can induce transient ovarian cancer persister cells characterized by low proliferation and paclitaxel tolerance, and tolerant persister cells show increased mitochondrial FAO.

Sep 29, 2026

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