ArticleNature cancer2022
Therapeutic targeting of the mevalonate-geranylgeranyl diphosphate pathway with statins overcomes chemotherapy resistance in small cell lung cancer.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- The Influence of Statin Use on Chemotherapeutic Efficacy in Studies of Mouse Models: A Systematic Review.Anticancer research · 2023Pooled it
- Efficacy and safety of albumin-bound paclitaxel combined with simvastatin in the second-line treatment of small cell lung cancer: a phase II randomized controlled trial.BMC medicine · 2026Trial
- Geranylgeranylation is required for B-cell proliferation and plasma cell survival implications for autoimmune therapy.Cellular & molecular immunology · 2026Article
- Lipid Metabolic Reprogramming in Lung Cancer: Mechanisms and Therapeutic Targets in the Tumor Microenvironment.International journal of cancer · 2026Review
- A synergistic cascade nanoreactor breaks bladder cancer chemoresistance: Synergizing cholesterol metabolism reprogramming with cGAS-STING-mediated metallotherapy.Materials today. Bio · 2026Article
- Statins and Myasthenia Gravis: Clinical Implications and Pathogenesis.International journal of molecular sciences · 2026Review
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Mechanism of lovastatin in promoting ferroptosis of prostate cancer cells by regulating the mevalonate pathway.European journal of histochemistry : EJH · 2026Article
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer.Nature communications · 2026Article
- Mevalonate pathway rewiring driven by enhancer remodelling confers resistance to KRAS inhibitors in colorectal cancer.Nature communications · 2026Article
- Simvastatin Restores Cisplatin Sensitivity by Suppressing the Caveolin-1-Mediated PI3K/AKT Signaling Pathway in Cisplatin-Resistant Cervical Cancer Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Lipophilic Statins Deplete GPX4 to Promote Ferroptosis and Sensitize Cancer Cells to Immune Checkpoint Blockade.Molecular cancer therapeutics · 2026Article
- Statins targeting mevalonate-geranylgeranyl diphosphate pathway inhibit proliferation in NK/T lymphoma by promoting pyroptosis.Translational oncology · 2026Article
- Profiling the tumor-resident microbiota in small cell lung cancer and its influence on clinical outcomes.Journal of translational medicine · 2026Article
- ALDH1L2 induces resistance to chemotherapy in small cell lung cancer by inhibiting ferroptosis.Redox biology · 2026Article
- Targeting cholesterol-driven immunometabolism in cancer: from molecular circuits to clinical translation.Molecular cancer · 2026Review
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small cell lung cancer (SCLC) lacks effective treatments to overcome chemoresistance. Here we established multiple human chemoresistant xenograft models through long-term intermittent chemotherapy, mimicking clinically relevant therapeutic settings. We show that chemoresistant SCLC undergoes metabolic reprogramming relying on the mevalonate (MVA)-geranylgeranyl diphosphate (GGPP) pathway, which can be targeted using clinically approved statins. Mechanistically, statins induce oxidative stress accumulation and apoptosis through the GGPP synthase 1 (GGPS1)-RAB7A-autophagy axis. Statin treatment overcomes both intrinsic and acquired SCLC chemoresistance in vivo across different SCLC PDX models bearing high GGPS1 levels. Moreover, we show that GGPS1 expression is negatively associated with survival in patients with SCLC. Finally, we demonstrate that combined statin and chemotherapy treatment resulted in durable responses in three patients with SCLC who relapsed from first-line chemotherapy. Collectively, these data uncover the MVA-GGPP pathway as a metabolic vulnerability in SCLC and identify statins as a potentially effective treatment to overcome chemoresistance.
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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 OpenQuestion graph.