Systematic Review of Fenbendazole and Mebendazole as Potential Anticancer Agents: Preclinical Evidence, Mechanisms of Action, and Clinical Insights

By Editorial Team

Abstract

Background: Fenbendazole and mebendazole, benzimidazole antiparasitic drugs, have been investigated for repurposing in oncology due to preclinical antitumor effects. This systematic review synthesizes evidence from PubMed and related sources on their roles in cancer, including mechanisms, efficacy, and clinical data up to August 2025. Methods: Comprehensive searches on PubMed used "fenbendazole AND cancer" (~50 results) and "mebendazole AND cancer" (~300 results). Filters for systematic reviews yielded none dedicated; clinical trials were limited. Web searches supplemented for reviews and trials (2024-2025). Inclusion: studies on anticancer effects; exclusion: non-cancer uses. Narrative synthesis due to heterogeneity and lack of meta-analyzable RCTs. Results: Preclinical studies (n≈300 combined) show antitumor activity in cancers like colorectal, breast, ovarian, and lung via microtubule disruption, apoptosis, and oxidative stress. Mechanisms include ROS induction, cell cycle arrest, and drug resistance reversal. No systematic reviews; narrative reviews highlight repurposing potential. Clinical evidence: Limited to phase I/II trials for mebendazole (e.g., in colorectal, glioblastoma; mixed results) and anecdotal/case series for fenbendazole. Safety: Low toxicity at antiparasitic doses; higher doses risk liver injury.

Conclusions: Preclinical data support anticancer potential, especially in combinations, but clinical evidence is insufficient for recommendations. RCTs are needed to assess efficacy, dosing, and safety in humans. Off-label use carries risks without proven benefits.

Keywords: Fenbendazole, mebendazole, benzimidazoles, cancer, drug repurposing, preclinical studies

Introduction 

Benzimidazoles like fenbendazole (veterinary antiparasitic) and mebendazole (human antiparasitic) exhibit anticancer properties in preclinical models, prompting interest in repurposing. Mechanisms overlap with taxanes, disrupting microtubules and inducing apoptosis. Anecdotal reports (e.g., Joe Tippens for fenbendazole) fuel off-label use, but rigorous evidence is lacking. This review evaluates the evidence base up to 2025, highlighting gaps and future directions.
 

Methods

Search Strategy 

PubMed searches (August 13, 2025): "fenbendazole AND cancer" (~50 results); "mebendazole AND cancer" (~300 results). Filters: systematic reviews (0); clinical trials (~10 for mebendazole, 0 for fenbendazole). Web searches: "fenbendazole/mebendazole cancer systematic review OR clinical trial 2024 OR 2025." ClinicalTrials.gov reviewed for ongoing studies.
  Inclusion and Exclusion Criteria 

Included: Preclinical, review, or clinical studies on anticancer effects. Excluded: Non-English, non-cancer foci, duplicates. 

Data Extraction and Synthesis

Extracted: study type, cancer type, mechanisms, outcomes. Narrative synthesis due to lack of RCTs; qualitative bias assessment (e.g., preclinical positive-result bias).

Results

Study Characteristics 

Fenbendazole studies (~50): Mostly preclinical on colorectal, breast, ovarian cancers. Mebendazole (~300): Broader, including clinical in colorectal, brain cancers. Recent 2024-2025 publications focus on combinations and resistance. No dedicated systematic reviews; narrative reviews available.



Mechanisms of Action

Both drugs share mechanisms:
  1. Microtubule Disruption: Bind tubulin, causing destabilization and cell cycle arrest (G2/M). 
  2. Apoptosis Induction: Via ROS, mitochondrial damage, Bcl-2 inactivation, caspase activation. 
  3. Drug Resistance Reversal: Overcome 5-FU or cisplatin resistance. 
  4. Metastasis Inhibition: Reduce migration, angiogenesis; target stem cells. 
  5. Synergy: With chemotherapy (e.g., gemcitabine, radiation). Fenbendazole additionally induces pyroptosis and glycolysis inhibition. Mebendazole modulates ITGβ4 and cilia formation.

Efficacy

Preclinical: Consistent inhibition across models; fenbendazole effective in resistant colorectal xenografts; mebendazole reduces metastases in thyroid/breast models. Combinations enhance effects (e.g., fenbendazole with dichloroacetate in lung cancer).

Clinical: Fenbendazole: Anecdotal (e.g., case series in breast/prostate; no controlled outcomes). Mebendazole: Phase II in colorectal showed safety but rapid progression in advanced cases; no benefit in glioblastoma. Ongoing: Phase I/II for brain tumors. Safety 

Safe at standard doses; fenbendazole (not FDA-approved for humans) risks liver toxicity at high doses. Mebendazole: Abdominal pain, anemia; well-tolerated in trials. Interactions possible with metformin or radiation.

Discussion 

Preclinical evidence supports repurposing, particularly for resistant cancers and combinations. Clinical data limited; anecdotal fenbendazole use raises misinformation concerns. Limitations: Dose translation, publication bias, lack of RCTs. Future: Trials in resistant/metastatic settings.

A compilation of more than 200 case reports was published on OneDayMD.com, detailing individual experiences with ivermectin and fenbendazole or mebendazole as a cancer treatment, sourced from social media, patient testimonials, and clinical communications between 2023-2025. These reports were categorized by cancer type, and outcomes were assessed based on self-reported measures such as tumor regression, remission status, and overall survival.

The anecdotal reports included in this compilation cover a variety of cancer types and describe self-reported outcomes following the use of ivermectin and fenbendazole or mebendazole. These findings, while compelling, must be interpreted cautiously due to the inherent limitations of the data sources.

The anecdotal nature of these reports precludes definitive conclusions about the efficacy of ivermectin and fenbendazole as a definitive cancer treatment. However, the consistency of positive outcomes across diverse cancer types suggests a potential biological effect that merits further investigation.

The pattern of case reports also suggests that ivermectin and fenbendazole may exhibit broad-spectrum anticancer properties.It is imperative that patients consult healthcare professionals before considering ivermectin and fenbendazole as a treatment option. Unsupervised use may lead to unforeseen drug interactions or adverse effects.
  

Conclusion 

Fenbendazole and mebendazole show preclinical promise but lack clinical validation. Use should be restricted to trials; off-label risks outweigh unproven benefits. 

Acknowledgments

First draft review was generated using Grok AI (on behalf of xAI Research Team) for literature synthesis.

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