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Triple Combination Of Ivermectin, Mebendazole and Fenbendazole For Cancer. Abstract✅Background: Drug repurposing is gaining attention in oncology. Antiparasitic agents such as ivermectin, fenbendazole, and mebendazole have demonstrated preclinical anticancer activity. The potential synergy of these agents as a triple combination is of increasing interest.✅Objective: To review mechanistic rationale, preclinical evidence, and human observational data supporting the triple combination of ivermectin, fenbendazole, and mebendazole in cancer and discuss research gaps and limitations.✅Methods:Mechanistic studies, preclinical research, and publicly reported case testimonials were reviewed. Human evidence was synthesized using a PRISMA-style framework.✅Results: Preclinical studies demonstrate complementary mechanisms of action across all three agents. 10 publicly reported cases of triple anti-parasitic therapy and one case of quadruple anti-parasitic therapy suggest temporal associations with tumor shrinkage or biomarker improvements, though all are uncontrolled and confounded by prior or concurrent therapies.✅Conclusion: While biologically plausible, the ivermectin–fenbendazole–mebendazole combination remains investigational. Observations are hypothesis-generating and warrant controlled preclinical studies and exploratory clinical trials before clinical adoption✅Mechanistic Rationale: The Triple Combination ApproachThe triple combination is based on complementary anticancer mechanisms:➡️Microtubule Disruption: Fenbendazole and Mebendazole inhibit microtubule polymerization, leading to mitotic arrest and apoptosis (programmed cell death) (OneDayMD, 2026).➡️Metabolic Interference: Fenbendazole impairs glucose uptake via GLUT1/hexokinase inhibition, effectively disrupting the energy supply of cancer cells.➡️Oncogenic Signaling Inhibition: Ivermectin targets STAT3, Wnt/β-catenin, AKT/mTOR, and YAP pathways, potentially enhancing programmed cell death and immune modulation.➡️Anti-angiogenic Activity: Mebendazole suppresses VEGF-mediated angiogenesis, limiting the tumor's ability to form new blood vessels.➡️Cancer Stem Cell Targeting: Both Mebendazole and Ivermectin may reduce tumor recurrence and drug resistance by targeting cancer stem cells.➡️Pharmacokinetic Complementarity: Mebendazole has better-established human dosing and bioavailability, while Fenbendazole is widely available and increasingly reported in anecdotal clinical cases.This multi-axis interference underpins the hypothesis that the triple combination may produce synergistic anticancer effects.