ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Targeting AKR1B10 by Drug Repurposing with Epalrestat Overcomes Chemoresistance in Non-Small Cell Lung Cancer Patient-Derived Tumor Organoids.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- 4-Hydroxytamoxifen induces a noncanonical ferroptosis in lung adenocarcinoma by targeting AKR1B10.Clinical and translational medicine · 2026Article
- Patient-Derived Organoid and Single-Cell Multiomics Reveal Evolution Driven by CEACAM6/KRT19-Mediated Heterogeneity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- [Standardized Construction of Lung Cancer Organoids and Their Application Progress in the Precise Treatment of Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Single-cell and multi-omics integration delineates the landscape of gene-wise intratumor heterogeneity and identifies prognostic biomarkers for immunotherapy in non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Patient-Derived Lung Cancer Organoids for Precision Oncology: A Comprehensive Analysis.JTO clinical and research reports · 2026Article
- AKR1B10 reprograms neutrophils by histone lactylation to foster immune evasion in KRASJournal of experimental & clinical cancer research : CR · 2026Article
- Characterization of a bronchoscopically induced transgenic lung cancer pig model for human translatability.Lab animal · 2026Article
- Genomic innovations in cancer prevention, diagnosis, prognosis and precision therapeutics.Frontiers in genetics · 2026Review
- A vascularized 3D bioengineered lung tumor model for anticancer drug screening.Cancer cell international · 2025Article
- NKX2-1 Restricts the Growth and Metastasis of Lung Squamous Cell Carcinoma Through Transcriptive Suppression of AKR1B10.Journal of biochemical and molecular toxicology · 2025Article
- Lung cancer organoids: a new strategy for precision medicine research.Translational lung cancer research · 2025Review
- Epalrestat Alleviates Reactive Oxygen Species and Endoplasmic Reticulum Stress by Maintaining Glycosylation in IMS32 Schwann Cells Under Exposure to Galactosemic Conditions.International journal of molecular sciences · 2025Article
- RGD-Modified Gold Nanoparticles Loaded with SAHA Remodel the Hypoxic Inflammatory Microenvironment via Inhibiting HIF-1α-VEGF Signaling to Enhance Radiosensitivity in NSCLC.International journal of nanomedicine · 2025Article
- Aldo-keto reductase family 1 member B10 prevents esophageal squamous cell carcinoma from reactive carbonyl species-induced cell death and promotes its progression.Cancer cell international · 2024Article
- Non-small cell lung cancer organoids: Advances and challenges in current applications.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
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14 authors.
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Abstract
purposeSystemic treatments given to patients with non-small cell lung cancer (NSCLC) are often ineffective due to drug resistance. In the present study, we investigated patient-derived tumor organoids (PDTO) and matched tumor tissues from surgically treated patients with NSCLC to identify drug repurposing targets to overcome resistance toward standard-of-care platinum-based doublet chemotherapy. EXPERIMENTAL
designPDTOs were established from 10 prospectively enrolled patients with non-metastatic NSCLC from resected tumors. PDTOs were compared with matched tumor tissues by histopathology/immunohistochemistry, whole exome sequencing, and transcriptome sequencing. PDTO growths and drug responses were determined by measuring 3D tumoroid volumes, cell viability, and proliferation/apoptosis. Differential gene expression analysis identified drug-repurposing targets. Validations were performed with internal/external data sets of patients with NSCLC. NSCLC cell lines were used for aldo-keto reductase 1B10 (AKR1B10) knockdown studies and xenograft models to determine the intratumoral bioavailability of epalrestat.
resultsPDTOs retained histomorphology and pathological biomarker expression, mutational/transcriptomic signatures, and cellular heterogeneity of the matched tumor tissues. Five (50%) PDTOs were chemoresistant toward carboplatin/paclitaxel. Chemoresistant PDTOs and matched tumor tissues demonstrated overexpression of AKR1B10. Epalrestat, an orally available AKR1B10 inhibitor in clinical use for diabetic polyneuropathy, was repurposed to overcome chemoresistance of PDTOs. In vivo efficacy of epalrestat to overcome drug resistance corresponded to intratumoral epalrestat levels.
conclusionsPDTOs are efficient preclinical models recapitulating the tumor characteristics and are suitable for drug testing. AKR1B10 can be targeted by repurposing epalrestat to overcome chemoresistance in NSCLC. Epalrestat has the potential to advance to clinical trials in patients with drug-resistant NSCLC due to favorable toxicity, pharmacological profile, and bioavailability.
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