Mebendazole or Fenbendazole

Are you a health professional?

This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Commentary

Integrative physician Will LaValley, MD, May 15, 2024: In some treatment plans I develop, mebendazole is included as a repurposed pharmaceutical among a group of repurposed pharmaceuticals. Repurposed pharmaceuticals in molecular integrative oncology (MIO) are important therapeutic options. MIO is inherently and fundamentally molecular-network medicine. Emphasis is on targeting molecular networks with multi-targeted repurposed drugs (and natural products) to target molecular networks in cancer cells, cancer stem cells, and tumor microenvironment cells.

The mechanism of action of benzimidazoles—mebendazole and fenbendazole—is through their interaction binding beta-tubulin and subsequent disruption of microtubule dynamics. This occurs in parasite cells and this occurs in cancer cells. Thus the re-purposing of these drugs is for similar molecular actions beneficial in a different clinical setting (anticancer).

Major classes of chemotherapy are administered to inhibit microtubule function. Inhibiting (stopping) normal microtubule function causes various cellular organelles to malfunction, leading to mitochondrial dysfunction, endoplasmic reticulum stress, disruption of mitotic spindle formation, induction of mitotic arrest, and subsequent apoptosis.

Microtubule inhibition by various conventional chemotherapies is major standard-of-care chemotherapy. Taxane chemotherapies (paclitaxel/docetaxel/cabazitaxel) target microtubule function by inhibiting the depolymerization of “already polymerized” microtubules. In other words, inhibition of microtubule function by inhibiting depolymerization is the major functional target of paclitaxel/docetaxel/cabazitaxel (taxanes).

Benzimidazoles (mebendazole and fenbendazole) target different binding sites on beta-tubulin than taxanes. Inhibition of microtubule “pre-polymerization” (benzimidazoles binding beta-tubulin) and inhibition of microtubule “post-polymerization” (taxanes binding the interior lumen of the microtubule) are two different mechanisms of action resulting in inhibition of microtubule function.

Other conventional chemotherapies—vinca alkaloids (vincristine, vinblastine, vinorelbine) and epothilones—also inhibit microtubule function.

The ability to inhibit microtubule dynamic function makes mebendazole a valuable option. Mebendazole and fenbendazole specifically target pre-polymerization inhibition of microtubule formation—thereby targeting the inhibition of cytoskeleton and other microtubule functions. This interaction leads to cell cycle arrest at the G2/M phase, inducing apoptosis in cancer cells. Its anticancer activity is cytotoxic to numerous cancer cell lines.

Large tumor load has large cytoskeleton demands and therefore large microtubule requirements. The anticancer molecular mechanism of mebendazole (and fenbendazole) has clinical importance. Consequently, the potential clinical value of the benzimidazoles mebendazole and fenbendazole through anti-microtubule molecular mechanism is a rational repurposing of the drugs. Dosage amount, frequency, duration, and repetition of dosage cycles are ripe for clinical trials and I know of none currently being funded.

Importantly, the safety profile of the benzimidazoles: in comparison to the taxanes, vinca alkaloids, and epothilones, benzimidazoles appear to be significantly better tolerated with significantly less adverse effect. Mebendazole at 4000 mg per day was found to be safe in a GI cancer (squamous cell cancer or adenocarcinoma, including primary cancer of the liver, of the gastrointestinal tract or cancer of unknown origin) for 16 weeks. However, all cases rapidly progressed and therefore no clinical benefit was identified. The rationale of combining this antimicrotubule therapy with additional anticancer repurposed drugs is important to consider in future trials.

One additional advantage of mebendazole is that it has relatively very few drug-drug interactions (most notably metronidazole—usually not an issue because the two drugs are not being recommended together in repurposed anticancer treatment) and is generally well tolerated.

Access and cost can be a major issue. Vermox is not readily available in many pharmacies. Some compounding pharmacies have mebendazole available.

Because fenbendazole is a veterinary drug, I do not make any recommendations for it due to professional restrictions from using veterinary drugs not approved for use in humans. Even so, the chemistry of fenbendazole and mebendazole are very similar and the molecular mechanisms of action are similar. It appears that fenbendazole may have more broad anticancer molecular targeting effects than mebendazole.

There are interesting papers regarding mebendazole and radiation therapy—including in TNBC. It has been shown to block cell cycle progression in radiotherapy-resistant TNBC cells by enhancing the anticancer effect of radiotherapy by blocking cell cycle progression, cell viability and colony formation, and inhibiting cell migration and invasion. It also has demonstrated enhancement of natural killer (NK) cell-mediated cytotoxicity in RT treatment.

Modes of action

Mebendazole inhibits signaling pathways: 

• Mebendazole inhibited the activity of three major kinases involved in cancer biology—ABL1, MAPK1/ERK2, and MAPK14/p38α—in vitro in a dose-dependent manner, with a high potency against MAPK14.¹Ariey-Bonnet J, Carrasco K et al. In silico molecular target prediction unveils mebendazole as a potent MAPK14 inhibitor. Molecular Oncology. 2020 Dec;14(12):3083-3099.
• Mebendazole downregulated USP5 expression and disrupted the interaction between USP5 and c-Maf, thus leading to increased levels of c-Maf ubiquitination and subsequent c-Maf degradation. Mebendazole inhibits c-Maf transcriptional activity, as confirmed by both luciferase assays and expression measurements of c-Maf downstream genes.²Chen XH, Xu YJ et al. Mebendazole elicits potent antimyeloma activity by inhibiting the USP5/c-Maf axis. Acta Pharmacologica Sinica. 2019 Dec;40(12):1568-1577
• Mebendazole inhibited S1P-induced cancer cell growth, and MBZ showed a growth inhibitory effect by regulating the JAK2/STAT3/Bcl-2 pathway.³Limbu KR, Chhetri RB, Oh YS, Baek DJ, Park EY. Mebendazole impedes the proliferation and migration of pancreatic cancer cells through SK1 inhibition dependent pathway. Molecules. 2022 Nov 22;27(23):8127.
• The novel IGF-1R inhibitor PB-020 combined with mebendazole potently suppressed the PI3K/AKT signaling pathway genes in colorectal cancer that may be associated with the development of drug resistance.⁴Kang B, Zhang X et al. The novel IGF-1R inhibitor PB-020 acts synergistically with anti-PD-1 and mebendazole against colorectal cancer. Cancers (Basel). 2022 Nov 23;14(23):5747.
• Mebendazole modulated the cancer-associated pathways including ELK1/SRF, AP1, STAT1/2, MYC/MAX.⁵Zhang F, Li Y et al. Anthelmintic mebendazole enhances cisplatin’s effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC). Oncotarget. 2017 Feb 21;8(8):12968-12982. 
• OBD9, an oxetane derivative of mebendazole, suppressed colorectal cancer growth by interfering with the Wnt signaling pathway, a main driver of cell growth in colorectal cancer.⁶Zhou K, Cheong JE et al. Inhibition of Wnt signaling in colon cancer cells via an oral drug that facilitates TNIK degradation. Molecular Cancer Therapeutics. 2023 Jan 3;22(1):25-36.
• The C-MYC gene as one of the pathways by which MBZ induces cell death in gastric cancer cells⁷Pinto LC, Mesquita FP et al. Mebendazole induces apoptosis via C-MYC inactivation in malignant ascites cell line (AGP01). Toxicology In Vitro. 2019 Oct;60:305-312.
• Mebendazole suppressed the Notch1 signaling pathway of a chemoresistant T cell acute lymphoblastic leukemia (T-ALL) cell line.⁸Wang X, Lou K et al. Mebendazole is a potent inhibitor to chemoresistant T cell acute lymphoblastic leukemia cells. Toxicology and Applied Pharmacology. 2020 Jun 1;396:115001. 
• Mebendazole potently inhibited Hh signaling of hedgehog (Hh)-driven human medulloblastoma cells at clinically attainable concentrations.⁹Larsen AR, Bai RY et al. Repurposing the antihelmintic mebendazole as a hedgehog inhibitor. Molecular Cancer Therapies. 2015 Jan;14(1):3-13.

Mebendazole also modulated tumor metabolism, ¹⁰da Silva EL, Mesquita FP et al. Mebendazole targets essential proteins in glucose metabolism leading gastric cancer cells to death. Toxicology and Applied Pharmacology. 2023 Sep 15;475:116630. potentiated the immune stimulatory and anticancer effects of peripheral blood mononuclear cells (PBMCs),¹¹Rubin J, Mansoori S et al. Mebendazole stimulates CD14+ myeloid cells to enhance T-cell activation and tumour cell killing. Oncotarget. 2018 Jul 20;9(56):30805-30813. and reduced integrin β4 (ITGβ4) expression and cancer stem cell properties.¹²Joe NS, Godet I et al. Mebendazole prevents distant organ metastases in part by decreasing ITGβ4 expression and cancer stemness. Breast Cancer Research. 2022 Dec 28;24(1):98. 

Mebendazole not only exhibited direct cytotoxic activity, but also synergized with ionizing radiation and different chemotherapeutic agents and stimulated antitumoral immune responses.¹³Guerini AE, Triggiani L et al. Mebendazole as a candidate for drug repurposing in oncology: an extensive review of current literature. Cancers (Basel). 2019 Aug 31;11(9):1284. 

Mebendazole and fenbendazole each inhibited microtubule formation.¹⁴De Witt M, Gamble A et al. Repurposing mebendazole as a replacement for vincristine for the treatment of brain tumors. Molecular Medicine. 2017 Apr;23:50-56; Dogra N, Kumar A, Mukhopadhyay T. Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways. Scientific Reports. 2018 Aug 9;8(1):11926. Flubendazole, another benzimidazole-based anthelmintic, also inhibited tubulin polymerization.¹⁵Spagnuolo PA, Hu J et al. The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma. Blood. 2010 Jun 10;115(23):4824-33; Hou ZJ, Luo X et al. Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells. Oncotarget. 2015 Mar 20;6(8):6326-40.

Mebendazole and albendazole induced classical apoptosis characterized by caspase-3 activation, phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane permeability, and reactive oxygen species production.¹⁶Petersen JSSM, Baird SK. Treatment of breast and colon cancer cell lines with anti-helmintic benzimidazoles mebendazole or albendazole results in selective apoptotic cell death. Journal of Cancer Research and Clinical Oncology. 2021 Oct;147(10):2945-2953.

Benzimidazole-based anthelmintics targeted genetic expression.¹⁷Garg A, Karhana S et al. Network pharmacology and molecular docking study-based approach to explore mechanism of benzimidazole-based anthelmintics for the treatment of lung cancer. Journal of Biomolecular Structure & Dynamics. 2023 Sep 23:1-22; Mrkvová Z, Uldrijan S, Pombinho A, Bartůněk P, Slaninová I. Benzimidazoles downregulate Mdm2 and MdmX and activate p53 in MdmX overexpressing tumor cells. Molecules. 2019 Jun 7;24(11):2152; Kim YJ, Sung D et al. Flubendazole overcomes trastuzumab resistance by targeting cancer stem-like properties and HER2 signaling in HER2-positive breast cancer. Cancer Letters. 2018 Jan 1;412:118-130.

Flubendazole induced autophagic cell death and promoted the up-regulation of EVA1A in triple-negative breast cancer cells in preclinical studies.¹⁸Zhen Y, Zhao R et al. Flubendazole elicits anti-cancer effects via targeting EVA1A-modulated autophagy and apoptosis in triple-negative breast cancer. Theranostics. 2020 Jul 2;10(18):8080-8097.

Resistance to mebendazole can be reversed partially by siRNA knockdown of cellular levels of XIAP.¹⁹Doudican NA, Byron SA, Pollock PM, Orlow SJ. XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts. Anticancer Drugs. 2013 Feb;24(2):181-8.

Preclinical evidence

Notable preclinical evidence is presented here; clinical evidence is summarized in How can mebendazole or fenbendazole help you? What the research says ›

Improving treatment outcomes

Cancer as a whole

Mebendazole inhibited VEGFR2 kinase activity²⁰Elmaaty AA, Darwish KM et al. In silico and in vitro studies for benzimidazole anthelmintics repurposing as VEGFR-2 antagonists: novel mebendazole-loaded mixed micelles with enhanced dissolution and anticancer activity. ACS Omega. 2021 Dec 22;7(1):875-899. as well as angiogenesis at doses comparable with its known effects on hookworm.²¹Dakshanamurthy S, Issa NT et al. Predicting new indications for approved drugs using a proteochemometric method. Journal of Medicinal Chemistry. 2012 Aug 9;55(15):6832-48. 

Advanced cancer as a whole

Mebendazole lowered cancer markers in malignant ascites cells.²²Pinto LC, Mesquita FP et al. Mebendazole induces apoptosis via C-MYC inactivation in malignant ascites cell line (AGP01). Toxicology In Vitro. 2019 Oct;60:305-312.

Brain and nervous system cancer

Glioblastoma

• An oleic acid and Labrafil M2125 formulation of mebendazole led to longer median survival in glioblastoma rat models.²³Mena-Hernández J, Jung-Cook H et al. Preparation and evaluation of mebendazole microemulsion for intranasal delivery: an alternative approach for glioblastoma treatment. AAPS PharmSciTech. 2020 Sep 27;21(7):264. 
• Mebendazole led to a significant increase in survival time of animals with GL261 orthotopic tumors.²⁴De Witt M, Gamble A et al. Repurposing mebendazole as a replacement for vincristine for the treatment of brain tumors. Molecular Medicine. 2017 Apr;23:50-56.
• Mebendazole inhibited glioblastoma cell proliferation, which was enhanced when adding chloroquine and then further enhanced by adding temozolomide.²⁵Jo SB, Sung SJ et al. Modulation of autophagy is a potential strategy for enhancing the anti-tumor effect of mebendazole in glioblastoma cells. Biomolecules & Therapeutics (Seoul). 2022 Nov 1;30(6):616-624.
• Mebendazole, fenbendazole, and flubendazole potently inhibited proliferation of glioblastoma multiforme cells.²⁶Ren LW, Li W et al. Benzimidazoles induce concurrent apoptosis and pyroptosis of human glioblastoma cells via arresting cell cycle. Acta Pharmacologica Sinica. 2022 Jan;43(1):194-208. 

Glioma

• Mebendazole and fenbendazole were cytotoxic in canine glioma cell lines.²⁷Lai SR, Castello SA, Robinson AC, Koehler JW. In vitro anti-tubulin effects of mebendazole and fenbendazole on canine glioma cells. Veterinary and Comparative Oncology. 2017 Dec;15(4):1445-1454.
• Mebendazole sensitized interphase glioma cells to the effects of ionizing radiation.²⁸Markowitz D, Ha G, Ruggieri R, Symons M. Microtubule-targeting agents can sensitize cancer cells to ionizing radiation by an interphase-based mechanism. OncoTargets and Therapy. 2017 Nov 24;10:5633-5642.
• Mebendazole displayed cytotoxicity and significantly extended mean survival syngeneic and xenograft orthotopic mouse glioma models.²⁹Bai RY, Staedtke V, Aprhys CM, Gallia GL, Riggins GJ. Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme. Neuro-oncology. 2011 Sep;13(9):974-82. 

Meningioma

• Mebendazole, either alone or combined with radiation, showed a survival benefit with an increase in apoptosis, and decreases in tumor cell and vascular proliferation in mice with human meningioma implants.³⁰Skibinski CG, Williamson T, Riggins GJ. Mebendazole and radiation in combination increase survival through anticancer mechanisms in an intracranial rodent model of malignant meningioma. Journal of Neuro-oncology. 2018 Dec;140(3):529-538.

Medulloblastoma

• Mebendazole slowed the growth of hedgehog (Hh)-driven human medulloblastoma cells at clinically attainable concentrations.³¹Larsen AR, Bai RY et al. Repurposing the antihelmintic mebendazole as a hedgehog inhibitor. Molecular Cancer Therapies. 2015 Jan;14(1):3-13.
• Mebendazole significantly slowed tumor growth and improved survival in 3 medulloblastoma animal models.³²Bodhinayake I, Symons M, Boockvar JA. Repurposing mebendazole for the treatment of medulloblastoma. Neurosurgery. 2015 Feb;76(2):N15-6.
• Mebendazole showed anticancer activity and significantly extended the survival of medulloblastoma models derived from different molecular backgrounds.³³Bai RY, Staedtke V, Rudin CM, Bunz F, Riggins GJ. Effective treatment of diverse medulloblastoma models with mebendazole and its impact on tumor angiogenesis. Neuro-oncology. 2015 Apr;17(4):545-54. 

Of three different mebendazole polymorphs (A, B, and C), C reaches therapeutically effective concentrations in the brain tissue and tumor with fewer side effects, and its efficacy can be further enhanced by combination with elacridar.³⁴Bai RY, Staedtke V et al. Brain penetration and efficacy of different mebendazole polymorphs in a mouse brain tumor model. Clinical Cancer Research. 2015 Aug 1;21(15):3462-3470.

Six benzimidazoles—flubendazole, parbendazole, oxibendazole, mebendazole, albendazole and fenbendazole—emerged as the most active compounds, with consistent antiproliferative effects across the tested cancer cell lines derived from paraganglioma.³⁵Florio R, Carradori S et al. Screening of benzimidazole-based anthelmintics and their enantiomers as repurposed drug candidates in cancer therapy. Pharmaceuticals (Basel). 2021 Apr 17;14(4):372. 

Breast cancer

Triple-negative breast cancer (TNBC)

• Mebendazole led to lower markers of triple-negative breast cancer and radiotherapy-resistant TNBC in mice.³⁶Choi HS, Ko YS et al. Anticancer effect of benzimidazole derivatives, especially mebendazole, on triple-negative breast cancer (tnbc) and radiotherapy-resistant TNBC in vivo and in vitro. Molecules. 2021 Aug 24;26(17):5118. 
• Mebendazole reduced the rate of lung metastases among rat models of radiotherapy-resistant triple-negative breast cancer treated radiotherapy without additional toxicity.³⁷Choi HS, Ko YS et al. Mebendazole increases anticancer activity of radiotherapy in radiotherapy-resistant triple-negative breast cancer cells by enhancing natural killer cell-mediated cytotoxicity. International Journal of Molecular Sciences. 2022 Dec 7;23(24):15493.
• Mebendazole-loaded/folic acid-targeted chitosan nanoparticles implanted subcutaneously led to smaller triple-negative breast tumor volume in mice.³⁸Kefayat A, Hosseini M, Ghahremani F, Jolfaie NA, Rafienia M. Biodegradable and biocompatible subcutaneous implants consisted of pH-sensitive mebendazole-loaded/folic acid-targeted chitosan nanoparticles for murine triple-negative breast cancer treatment. Journal of Nanobiotechnology. 2022 Mar 31;20(1):169.
• Mebendazole reduced TNBC cell proliferation, induced apoptosis, and caused G2/M cell cycle arrest. It also reduced the size of primary tumors and prevented lung and liver metastases.³⁹Joe NS, Godet I et al. Mebendazole prevents distant organ metastases in part by decreasing ITGβ4 expression and cancer stemness. Breast Cancer Research. 2022 Dec 28;24(1):98.
• In cell and animal studies, mebendazole showed several anticancer effects, including sensitizing TNBC cells to ionizing radiation.⁴⁰Zhang L, Bochkur Dratver M et al. Mebendazole potentiates radiation therapy in triple-negative breast cancer. International Journal of Radiation Oncology, Biology, Physics. 2019 Jan 1;103(1):195-207.

Mammary tumors

• Intensive treatments with fenbendazole were toxic to mouse mammary tumor cells in vitro but fenbendazole did not alter the dose-response curves for radiation or chemotherapy (docetaxel) of mammary tumors in mice.⁴¹Duan Q, Liu Y, Rockwell S. Fenbendazole as a potential anticancer drug. Anticancer Research. 2013 Feb;33(2):355-62. 
• Therapeutic levels of fenbendazole in the diet had no effect on tumor growth, invasion, or metastasis, nor any difference in radiation-induced tumor growth delay among mice implanted with mammary tumors.⁴²Duan Q, Liu Y, Booth CJ, Rockwell S. Use of fenbendazole-containing therapeutic diets for mice in experimental cancer therapy studies. Journal of the American Association for Laboratory Animal Science. 2012 Mar;51(2):224-30.

Flubendazole, another benzimidazole derivative, inhibited breast cancer cells proliferation and delayed tumor growth.⁴³Hou ZJ, Luo X et al. Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells. Oncotarget. 2015 Mar 20;6(8):6326-40; Kim YJ, Sung D et al. Flubendazole overcomes trastuzumab resistance by targeting cancer stem-like properties and HER2 signaling in HER2-positive breast cancer. Cancer Letters. 2018 Jan 1;412:118-130; Zhang L, Guo M et al. Systems biology-based discovery of a potential Atg4B agonist (Flubendazole) that induces autophagy in breast cancer. Molecular BioSystems. 2015 Nov;11(11):2860-6; Zhen Y, Zhao R et al. Flubendazole elicits anti-cancer effects via targeting EVA1A-modulated autophagy and apoptosis in triple-negative breast cancer. Theranostics. 2020 Jul 2;10(18):8080-8097.

Colorectal cancer

Colon cancer

• Mebendazole reduced tumor volume and weight and increased survival in mice bearing colon cancer.⁴⁴Aliabadi A, Haghshenas MR et al. In vitro and in vivo anticancer activity of mebendazole in colon cancer: a promising drug repositioning. Naunyn Schmiedeberg’s Archives of Pharmacology. 2024 Apr;397(4):2379-2388.
• Mebendazole showed anticancer activity in colon cancer cell lines,⁴⁵Nygren P, Fryknäs M, Agerup B, Larsson R. Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer. Journal of Cancer Research and Clinical Oncology. 2013 Dec;139(12):2133-40. selectively killing colorectal cancer cells.⁴⁶Petersen JSSM, Baird SK. Treatment of breast and colon cancer cell lines with anti-helmintic benzimidazoles mebendazole or albendazole results in selective apoptotic cell death. Journal of Cancer Research and Clinical Oncology. 2021 Oct;147(10):2945-2953.

Colorectal cancer

• Fenbendazole significantly induced apoptosis as well as cell cycle arrest in 5-fluorouracil-resistant colorectal cancer cells.⁴⁷Park D, Lee JH, Yoon SP. Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells. Korean Journal of Physiology & Pharmacology. 2022 Sep 1;26(5):377-387.
• Six benzimidazoles—flubendazole, parbendazole, oxibendazole, mebendazole, albendazole, and fenbendazole—emerged as the most active compounds, with consistent antiproliferative effects across the tested cancer cell lines derived from colorectal cancer.⁴⁸Florio R, Carradori S et al. Screening of benzimidazole-based anthelmintics and their enantiomers as repurposed drug candidates in cancer therapy. Pharmaceuticals (Basel). 2021 Apr 17;14(4):372; Králová V, Hanušová V, Rudolf E, Čáňová K, Skálová L. Flubendazole induces mitotic catastrophe and senescence in colon cancer cells in vitro. Journal of Pharmacy and Pharmacology. 2016 Feb;68(2):208-18; Pourgholami MH, Akhter J, Wang L, Lu Y, Morris DL. Antitumor activity of albendazole against the human colorectal cancer cell line HT-29: in vitro and in a xenograft model of peritoneal carcinomatosis. Cancer Chemotherapy and Pharmacology. 2005 May;55(5):425-32.

Gastrointestinal cancer

Gallbladder cancer 

• Mebendazole reduced cell proliferation in a cholangiocarcinoma cell line and slightly reduced the growth rate of subcutaneously xeno-grafted cancer of those same cell lines and increased apoptosis in nude mice.⁴⁹Sawanyawisuth K, Williamson T, Wongkham S, Riggins GJ. Effect of the antiparasitic drug mebendazole on cholangiocarcinoma growth. Southeast Asian Journal of Tropical Medicine and Public Health. 2014 Nov;45(6):1264-70. 

Intestinal cancer

• Albendazole and flubendazole inhibited intestinal cancer cell proliferation significantly.⁵⁰Králová V, Hanušová V et al. Antiproliferative effect of benzimidazole anthelmintics albendazole, ricobendazole, and flubendazole in intestinal cancer cell lines. Anticancer Drugs. 2013 Oct;24(9):911-9.

Liver cancer

• Mebendazole decreased AFP levels, improved liver function and histology, and increased survival in hepatocellular carcinoma (HCC) mice, particularly when administered in combination with sorafenib. It also showed other anticancer effects.⁵¹Younis NS, Ghanim AMH, Saber S. Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma. Scientific Reports. 2019 Dec 13;9(1):19095.
• Fenbendazole selectively suppressed the growth of hepatocellular carcinoma cells via p21-mediated cell cycle arrest at G1/S and G2/M, and resulted in apoptosis only in actively growing cells but not in quiescent cells.⁵²Park D. Fenbendazole suppresses growth and induces apoptosis of actively growing h4iie hepatocellular carcinoma cells via p21-mediated cell-cycle arrest. Biological & Pharmaceutical Bulletin. 2022;45(2):184-193.
• Fenbendazole, mebendazole, and albendazole showed cytotoxic activity against liver cancer cell lines.⁵³Elmaaty AA, Darwish KM et al. In silico and in vitro studies for benzimidazole anthelmintics repurposing as VEGFR-2 antagonists: novel mebendazole-loaded mixed micelles with enhanced dissolution and anticancer activity. ACS Omega. 2021 Dec 22;7(1):875-899.

Stomach cancer

• Mebendazole showed cytotoxicity in a human malignant ascites cell line derived from a primary gastric cancer tumor, and it also enhanced the cytotoxicity of 5-FU.⁵⁴Pinto LC, Soares BM et al. The anthelmintic drug mebendazole inhibits growth, migration and invasion in gastric cancer cell model. Toxicology In Vitro. 2015 Dec;29(8):2038-44.

Endocrine cancer

• Mebendazole significantly inhibited human adrenocortical carcinoma cancer cell growth and metastases formation in mice.⁵⁵Martarelli D, Pompei P, Baldi C, Mazzoni G. Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice. Cancer Chemotherapy and Pharmacology. 2008 Apr;61(5):809-17.

Head, neck, and oral cancer

Head and neck squamous cell carcinoma

• Mebendazole exerted more potent antiproliferation activity than cisplatin in human head and neck squamous cell carcinoma (HNSCC) cells. It synergized with cisplatin in suppressing cell proliferation and inducing apoptosis.⁵⁶Zhang F, Li Y et al. Anthelmintic mebendazole enhances cisplatin’s effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC). Oncotarget. 2017 Feb 21;8(8):12968-12982. 

Oral cancer

• Mebendazole and flubendazole reduced the viability of oral squamous carcinoma cells and of premalignant oral keratinocytes, but normal oral keratinocytes and normal gingival fibroblasts were less sensitive to the treatment.⁵⁷Kralova V, Hanušová V et al. Flubendazole and mebendazole impair migration and epithelial to mesenchymal transition in oral cell lines. ChemicoBiological Interactions. 2018 Sep 25;293:124-132.

Leukemia and other blood cancers

Leukemia

• Mebendazole extended survival of leukemia-bearing mice in a xenograft model.⁵⁸Li Y, Thomas D et al. Mebendazole for differentiation therapy of acute myeloid leukemia identified by a lineage maturation index. Scientific Reports. 2019 Nov 14;9(1):16775. 

T cell acute lymphoblastic leukemia

• Mebendazole suppressed the proliferation and reduced the viability of a chemoresistant T cell acute lymphoblastic leukemia (T-ALL) cell line. It also suppressed the growth of CEM/C1 cells in T-ALL mice models.⁵⁹Wang X, Lou K et al. Mebendazole is a potent inhibitor to chemoresistant T cell acute lymphoblastic leukemia cells. Toxicology and Applied Pharmacology. 2020 Jun 1;396:115001. 
• Mebendazole inhibited proliferation of adult T-cell leukemia/lymphoma (ATLL) cells.⁶⁰Maali A, Ferdosi-Shahandashti E, Sadeghi F, Aali E. The antihelminthic drug, mebendazole, induces apoptosis in adult T-cell leukemia/lymphoma cancer cells: in-vitro trial. International Journal of Hematology-Oncology and Stem Cell Research. 2020 Oct 1;14(4):257-264. 

Acute myeloid leukemia

• Mebendazole inhibited the growth of acute myeloid leukemia (AML) cell lines and bone marrow mononuclear cells from AML patients and showed other anticancer effects, but little inhibitory effect on the growth of normal peripheral blood mononuclear cells (PBMC) or human umbilical vein endothelial cells (HUVEC), at pharmacologically achievable concentrations.⁶¹He L, Shi L et al. Mebendazole exhibits potent anti-leukemia activity on acute myeloid leukemia. Experimental Cell Research. 2018 Aug 1;369(1):61-68.
• Mebendazole induced strong, dose-dependent anti-leukemic effects on AML cells, including the sensitization of AML cells to chemotherapy with cytarabine.⁶²Freisleben F, Modemann F et al. Mebendazole mediates proteasomal degradation of GLI transcription factors in acute myeloid leukemia. International Journal of Molecular Sciences. 2021 Oct 1;22(19):10670.

Leukemia and myeloma

• Flubendazole induced cell death in leukemia and myeloma cell lines and primary patient samples at nanomolar concentrations. Moreover, it delayed tumor growth in leukemia and myeloma xenografts without evidence of toxicity, and it synergized with vinblastine to reduce the viability of leukemia cells. Combinations of flubendazole with vinblastine or vincristine in a leukemia xenograft model delayed tumor growth more than either drug alone.⁶³Spagnuolo PA, Hu J et al. The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma. Blood. 2010 Jun 10;115(23):4824-33.

Lung cancer

Unspecified lung cancer

• Fenbendazole, mebendazole, and albendazole showed cytotoxic activity against lung cancer cell lines.⁶⁴Elmaaty AA, Darwish KM et al. In silico and in vitro studies for benzimidazole anthelmintics repurposing as VEGFR-2 antagonists: novel mebendazole-loaded mixed micelles with enhanced dissolution and anticancer activity. ACS Omega. 2021 Dec 22;7(1):875-899.
• Benzimidazole derivatives had cytotoxic effects on KRAS-mutant lung cancer cells.⁶⁵Shimomura I, Yokoi A et al. Drug library screen reveals benzimidazole derivatives as selective cytotoxic agents for KRAS-mutant lung cancer. Cancer Letters. 2019 Jun 1;451:11-22.

Non-small cell lung cancer

• Mebendazole caused mitotic arrest, followed by apoptotic cell death of non-small cell lung cancer cells. It elicited a strong antitumor effect in an animal model and reduced lung colonies in experimentally induced lung metastasis without any toxicity.⁶⁶Sasaki J, Ramesh R, Chada S, Gomyo Y, Roth JA, Mukhopadhyay T. The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. Molecular Cancer Therapeutics. 2002 Nov;1(13):1201-9.
• Fenbendazole induced endoplasmic reticulum stress, reactive oxygen species production, decreased mitochondrial membrane potential, and cytochrome c release that eventually led to cancer cell death in human non-small cell lung cancer cells.⁶⁷Dogra N, Mukhopadhyay T. Impairment of the ubiquitin-proteasome pathway by methyl N-(6-phenylsulfanyl-1H-benzimidazol- 2-yl)carbamate leads to a potent cytotoxic effect in tumor cells: a novel antiproliferative agent with a potential therapeutic implication. Journal of Biolological Chemistry. 2012 Aug 31;287(36):30625-40.

Pulmonary adenocarcinoma

• Mebendazole showed anti-neoplastic cytotoxicity against pulmonary adenocarcinoma cells as a single entity and contributed to the potency of dexamethasone-(C₂₁-phosphoramidate)-[anti-EGFR], a covalent immunoglucocorticoid.⁶⁸Coyne CP, Narayanan L. Mebendazole in simultaneous combination with dexamethasone-(C21-phosphoramidate)-[anti-EGFR] generated utilizing a novel synthesis regimen: dual anti-neoplastic cytotoxicity against pulmonary adenocarcinoma (A549). Journal of Experimental Therapeutics & Oncology. 2019 Dec;13(2):81-118.

Lung metastases

• Mebendazole strongly inhibited the growth of human tumor xenografts and significantly reduced the number and size of tumors in an animal model of lung metastasis.⁶⁹Mukhopadhyay T, Sasaki J, Ramesh R, Roth JA. Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo. Clinical Cancer Research. 2002 Sep;8(9):2963-9. 

Melanoma

• “In a human xenograft melanoma model, oral mebendazole is as effective as the current standard of care temozolomide in reducing tumor growth.”⁷⁰Doudican NA, Byron SA, Pollock PM, Orlow SJ. XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts. Anticancer Drugs. 2013 Feb;24(2):181-8.
• Systemic but not local flubendazole inhibited human melanoma growth and spread in mice, comparable to paclitaxel.⁷¹Li Y, Acharya G, Elahy M, Xin H, Khachigian LM. The anthelmintic flubendazole blocks human melanoma growth and metastasis and suppresses programmed cell death protein-1 and myeloid-derived suppressor cell accumulation. Cancer Letters. 2019 Sep 10;459:268-276.
• Mebendazole inhibited melanoma growth and preferentially induced apoptosis in melanoma cells compared with melanocytes.⁷²Doudican N, Rodriguez A, Osman I, Orlow SJ. Mebendazole induces apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells. Molecular Cancer Research. 2008 Aug;6(8):1308-15.
• Fenbendazole reduced viability in 5 canine melanoma cell lines.⁷³Kim S, Perera SK, Choi SI, Rebhun RB, Seo KW. G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells. Veterinary Medicine and Science. 2022 May;8(3):966-981. 
• Flubendazole induced apoptosis in melanoma cells.⁷⁴Rudolf K, Rudolf E. An analysis of mitotic catastrophe induced cell responses in melanoma cells exposed to flubendazole. Toxicology In Vitro. 2020 Oct;68:104930.
• Flubendazole inhibited cell growth and proliferation and disrupted microtubule structure and function in malignant melanoma cells.⁷⁵Čáňová K, Rozkydalová L, Vokurková D, Rudolf E. Flubendazole induces mitotic catastrophe and apoptosis in melanoma cells. Toxicology In Vitro. 2018 Feb;46:313-322.

Ovarian cancer

• Mebendazole inhibited growth of ovarian cancer cell cultures.⁷⁶Elayapillai S, Ramraj S et al. Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer. Gynecologic Oncology. 2021 Jan;160(1):302-311.
• Fenbendazole reduced epithelial ovarian cancer cell viability, and fenbendazole-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles reduced cell viability and increased apoptosis of EOC cells in mice, although unencapsulated fenbendazole did not.⁷⁷Chang CS, Ryu JY et al. Anti-cancer effect of fenbendazole-incorporated PLGA nanoparticles in ovarian cancer. Journal of Gynecologic Oncology. 2023 Sep;34(5):e58.

Pancreatic cancer

• Mebendazole reduced pancreas weight, dysplasia, intraepithelial neoplasia formation, and severity of liver metastasis, and it suppressed tumor growth in an aggressive mouse model of advanced pancreatic cancer.⁷⁸Williamson T, de Abreu MC et al. Mebendazole disrupts stromal desmoplasia and tumorigenesis in two models of pancreatic cancer. Oncotarget. 2021 Jul 6;12(14):1326-1338. 
• Mebendazole inhibited the proliferation and migration of cancer cells in pancreatic ductal adenocarcinoma (PDAC) cell lines.⁷⁹Limbu KR, Chhetri RB, Oh YS, Baek DJ, Park EY. Mebendazole impedes the proliferation and migration of pancreatic cancer cells through SK1 inhibition dependent pathway. Molecules. 2022 Nov 22;27(23):8127.
• Six benzimidazoles—flubendazole, parbendazole, oxibendazole, mebendazole, albendazole, and fenbendazole—emerged as the most active compounds, with consistent antiproliferative effects across the tested cancer cell lines derived from pancreatic cancer.⁸⁰Florio R, Carradori S, Veschi S, Brocco D, Di Genni T, Cirilli R, Casulli A, Cama A, De Lellis L. Screening of benzimidazole-based anthelmintics and their enantiomers as repurposed drug candidates in cancer therapy. Pharmaceuticals (Basel). 2021 Apr 17;14(4):372. 

Peritoneal cancer

• Albendazole inhibited tumor growth in mice with peritoneal xenografts of human colorectal origin.⁸¹Pourgholami MH, Akhter J, Wang L, Lu Y, Morris DL. Antitumor activity of albendazole against the human colorectal cancer cell line HT-29: in vitro and in a xenograft model of peritoneal carcinomatosis. Cancer Chemotherapy and Pharmacology. 2005 May;55(5):425-32.

Prostate cancer

• Fenbendazole enhanced antitumor activity against metastatic prostate cancer cells, and enhanced formulations as micelles or nanoparticles led to longer survival than paclitaxel treatment in mice bearing metastases. Fenbendazole effectively targeted taxane-resistant tumors and bone metastases.⁸²Chung I, Zhou K et al. Unbiased phenotype-based screen identifies therapeutic agents selective for metastatic prostate cancer. Frontiers in Oncology. 2021 Mar 2;10:594141. 
• Flubendazole inhibited cell proliferation, caused cell cycle arrest in G2/M phase and promoted cell death in vitro, and suppressed growth of castration-resistant prostate cancer tumors in xenograft models.⁸³Zhou X, Zou L et al. Flubendazole, FDA-approved anthelmintic, elicits valid antitumor effects by targeting P53 and promoting ferroptosis in castration-resistant prostate cancer. Pharmacological Research. 2021 Feb;164:105305.

Sarcoma

• Mebendazole showed no anticancer effects against fibrosarcoma in hamsters.⁸⁴Banovic P, Stankov S, Vranjes N, Zurkovic O, Capo I, Lalosevic D. Drug repurposing: mebendazole as effective antitumor agent. Are we seeing the whole story? Journal of BUON. 2018 Nov-Dec;23(6):1904-1911.

Thyroid cancer

• Mebendazole inhibited the growth of thyroid cancer cells, and it showed anticancer effects and prevented established thyroid tumors from metastasizing to the lung in mice.⁸⁵Williamson T, Mendes TB, Joe N, Cerutti JM, Riggins GJ. Mebendazole inhibits tumor growth and prevents lung metastasis in models of advanced thyroid cancer. Endocrine-related Cancer. 2020 Mar;27(3):123-136.

Mebendazole or fenbendazole combined with other therapies

Vinblastine plus mebendazole with temozolomide

• Combination treatment of vinblastine plus mebendazole with temozolomide (TMZ) was more effective in reducing glioblastoma cell number in most cultures when compared to TMZ alone, especially in cells with low expression levels of FGFR3 and AKT2.⁸⁶Kipper FC, Silva AO et al. Vinblastine and antihelmintic mebendazole potentiate temozolomide in resistant gliomas. Investigational New Drugs. 2018 Apr;36(2):323-331.

Novel IGF-1R inhibitor PB-020 and mebendazole

• The novel IGF-1R inhibitor PB-020 can act synergistically with mebendazole to reduce the viability of colorectal (CRC) cells and block xenograft CRC progression.⁸⁷Kang B, Zhang X et al. The novel IGF-1R inhibitor PB-020 acts synergistically with anti-PD-1 and mebendazole against colorectal cancer. Cancers (Basel). 2022 Nov 23;14(23):5747.

Fenbendazole plus vitamins A, D, E, K, and B

• Fenbendazole plus vitamins A, D, E, K, and B led to less tumor growth of lymphoma cells in mice.⁸⁸Gao P, Dang CV, Watson J. Unexpected antitumorigenic effect of fenbendazole when combined with supplementary vitamins. Journal of the American Association for Laboratory Animal Science. 2008 Nov;47(6):37-40.

Mebendazole with trametinib

• Mebendazole synergized with the MEK inhibitor trametinib to inhibit growth of BRAFWT-NRASQ61K melanoma cells in culture and in xenografts, markedly decreased MEK and ERK phosphorylation, and increased apoptosis.⁸⁹Simbulan-Rosenthal CM, Dakshanamurthy S et al. The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory nrasq61k melanoma. Oncotarget. 2017 Feb 21;8(8):12576-12595. 

Mebendazole and docetaxel

• Mebendazole and docetaxel increased apoptosis and reduced tumor growth of prostate cancer cells.⁹⁰Rushworth LK, Hewit K et al. Repurposing screen identifies mebendazole as a clinical candidate to synergise with docetaxel for prostate cancer treatment. British Journal of Cancer. 2020 Feb;122(4):517-527. 

Mebendazole and gemcitabine

• Mebendazole enhanced levels of cytotoxic anti-neoplastic activity of gemcitabine in chemotherapeutic-resistant mammary adenocarcinoma.⁹¹Coyne CP, Jones T, Bear R. Gemcitabine-(C₄–amide)-[anti-HER2/neu] anti-neoplastic cytotoxicity in dual combination with mebendazole against chemotherapeutic-resistant mammary adenocarcinoma. Journal of Clinical & Experimental Oncology. 2013;2(2):1000109.

Fenbendazole and rapamycin

• Fenbendazole and rapamycin substantially suppressed ovarian cancer tumor cell growth in cell studies.⁹²Shin YB, Choi JY, Shin DH, Lee JW. Anticancer evaluation of methoxy poly(ethylene glycol)- b-poly(caprolactone) polymeric micelles. International Journal of Nanomedicine. 2023 May 1;18:2209-2223.

Optimizing your body terrain

Inflammation

• Mebendazole reduced inflammation in mouse models of early pancreatic cancer.⁹³Williamson T, de Abreu MC et al. Mebendazole disrupts stromal desmoplasia and tumorigenesis in two models of pancreatic cancer. Oncotarget. 2021 Jul 6;12(14):1326-1338. 
• Fenbendazole lowered circulating plasma cytokines in Giardia-infected squirrel monkeys.⁹⁴Nehete PN, Wilkerson G et al. Cellular immune responses in peripheral blood lymphocytes of Giardia infected squirrel monkey (Saimiri boliviensis boliviensis) treated with fenbendazole. PLoS One. 2018 Nov 9;13(11):e0198497. 

Immune function

• Fenbendazole lowered numbers of total leukocytes, neutrophils, monocytes, and eosinophils in Giardia-infected squirrel monkeys.⁹⁵Nehete PN, Wilkerson G et al. Cellular immune responses in peripheral blood lymphocytes of Giardia infected squirrel monkey (Saimiri boliviensis boliviensis) treated with fenbendazole. PLoS One. 2018 Nov 9;13(11):e0198497. 
• Prophylactic fenbendazole administered in feed did not interfere with immune responses in mice.⁹⁶Reiss CS, Herrman JM, Hopkins RE 2nd. Effect of anthelminthic treatment on the immune response of mice. Laboratory Animal Science. 1987 Dec;37(6):773-5.

Oxidative stress

• Fenbendazole significantly suppressed oxidative stress in normal breast epithelial cells, but highly metastatic triple-negative adenocarcinoma cells were more vulnerable to fenbendazole-induced oxidative stress.⁹⁷Semkova S, Nikolova B et al. Redox-mediated anticancer activity of anti-parasitic drug fenbendazole in triple-negative breast cancer cells. Anticancer Research. 2023 Mar;43(3):1207-1212.
• Mebendazole and fenbendazole protected neurons against oxidative stress in a glutathione depletion model of oxidative stress.⁹⁸Aleyasin H, Karuppagounder SS et al. Antihelminthic benzimidazoles are novel HIF activators that prevent oxidative neuronal death via binding to tubulin. Antioxidants & Redox Signaling. 2015 Jan 10;22(2):121-34. 

Mebendazole or fenbendazole combined with other therapies

A short-course multimodal therapy of enrofloxacin, azithromycin, fenbendazole, and paromomycin to eliminate common macaque endemic pathogens led to less local and systemic innate and adaptive inflammation in clinically healthy macaques.⁹⁹Bochart RM, Busman-Sahay K et al. Mitigation of endemic GI-tract pathogen-mediated inflammation through development of multimodal treatment regimen and its impact on SIV acquisition in rhesus macaques. PLoS Pathogens. 2021 May 10;17(5):e1009565.

Reducing cancer risk

Brain and nervous system cancer

• Mebendazole inhibited the growth of neurofibromatosis 1 (NF1)-related malignant peripheral nerve sheath tumors, substantially delayed the formation of solid malignancies, and increased median survival. It enhanced the chemopreventive effect of the COX-2 inhibitor celecoxib (CXB) in mice.¹⁰⁰Staedtke V, Gray-Bethke T, Riggins GJ, Bai RY. Preventative effect of mebendazole against malignancies in neurofibromatosis 1. Genes (Basel). 2020 Jul 8;11(7):762.

Colorectal cancer

• Mebendazole showed anticancer effects in mouse models of familial adenomatous polyposis (FAP), including decreased COX2 expression, blood vessel formation, VEGFR2 phosphorylation. It also reduced the number of intestinal adenomas, and this reduction was substantially stronger when mebendazole was used with sulindac.¹⁰¹Williamson T, Bai RY, Staedtke V, Huso D, Riggins GJ. Mebendazole and a non-steroidal anti-inflammatory combine to reduce tumor initiation in a colon cancer preclinical model. Oncotarget. 2016 Oct 18;7(42):68571-68584.

Pancreatic cancer

• Mebendazole reduced the incidence of pancreatic cancer in mice.¹⁰²Williamson T, de Abreu MC et al. Mebendazole disrupts stromal desmoplasia and tumorigenesis in two models of pancreatic cancer. Oncotarget. 2021 Jul 6;12(14):1326-1338.