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  • Targeting Metabolic Vulnerabilities in Cancer: From the Warburg Effect to Antiparasitic Drug Repurposing

  • HOOSHANG HOSSEINPOUR,1,*
    1. Department of Biology, SR.C., Islamic Azad University, Tehran, Iran


  • Introduction: Cancer remains a leading cause of death, with conventional treatments limited by toxicity and resistance. Cancer cells exhibit metabolic reprogramming, including aerobic glycolysis (the Warburg effect) and dependence on mitochondrial substrate-level phosphorylation (SLP), which distinguishes them from normal cells and is shared with parasites, suggesting antiparasitic drugs could be repurposed as anticancer agents.
  • Methods: This narrative review systematically searched PubMed, Scopus, and Google Scholar for studies published between 2015 and 2026 on cancer metabolism, the Warburg effect, SLP, and antiparasitic drugs. From 45 selected articles, data on molecular mechanisms, preclinical, and clinical evidence were extracted and analyzed.
  • Results: Cancer cells display high glycolytic flux and SLP dependence, creating a therapeutic vulnerability. Mebendazole disrupts microtubules and inhibits SLP. Fenbendazole downregulates GLUT transporters, reducing glycolytic flux. Ivermectin inhibits AKT/mTOR signaling and induces mitochondrial dysfunction. Preclinical studies show tumor growth inhibition in glioblastoma, colorectal, breast, and pancreatic cancer models. Advantages include lower toxicity, oral bioavailability, low cost, and availability as generics, though large-scale clinical trials are lacking.
  • Conclusion: Repurposing antiparasitic drugs to target shared metabolic vulnerabilities offers a novel, low-cost, low-toxicity cancer therapy strategy. Despite promising preclinical results, clinical translation requires large-scale trials, optimal dosing, predictive biomarkers, and combination with standard therapies. This paradigm may shift oncology toward metabolism-based precision medicine.
  • Keywords: Cancer Metabolism, Drug Repurposing, Warburg Effect, Mitochondrial SLP, Antiparasitic Drugs

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