Ivermectin, an insecticide with very few side effects, has been shown to block numerous cancer signaling pathways in many cancers, reducing drug resistance, increasing drug effectiveness; in particular it damages and blocks Cancer Stem Cell activity.
There is also a combination anti-cancer protocol with Fenbendazole and/or Mebendazole. None of these drugs is yet approved for treating cancer by the WHO. (article originally published in 2018, and updated frequently by Chris Woollams M.A Biochemistry, Oxford University).
There is no Human Clinical Trial Evidence and therefore there are no proven dose levels for its use in cancer. And while we list below mulitiple laboratory studies demonstrating that ivermectin can inhibit cancer cell and cancer stem cell proliferation, and induce cell death through multiple mechanisms, we can only conclude that Ivernectin has the potential to treat cancer.
The Truth about Ivermectin - an overview
Ivermectin, or IVM, is approved as an insecticide; it is also an antiparasitic drug, an anthelmintic (it treats roundworms), and is widely used for the treatment of diseases such as scabies, river blindness and elephantiasis.
Satoshi Omura (Japan) and William C. Campbell (Ireland) won the 2015 Nobel Prize in Physiology or Medicine for their discovery of Ivermectin as it is extracted from Streptomyces avermitilis, a rare bacterium found in Japanese soil.
Ivermectin was discovered in 1975 and it was first approved for use in veterinary medicine to prevent and treat heartworm and acariasis.
it was approved by the FDA for use in humans as long ago as 1978, and has an excellent safety record (1). It is part of the Avermectin family, with few side-effects.
It has been used to treat a multitude of infestations such as, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis, head lice, scabies and lymphatic filariasis.
It is also potentially a good anti-viral. It has been shown to have 'robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus and SARS-CoV-2 (COVID-19). Ivermectin was used for example with success against West Nile Virus in Africa (17), As controversial as it may seem to some people, 'The African Enigma' points to Ivermectin likely being responsible for 8% less cases of Covid-19 and 28% less deaths from Covid-19. The World Health Organization (WHO) had sponsored the African Programme for Onchocerciasis Control (APOC) using Ivermectin in 19 countries from 1995 until 2015, and these were compared with thirty-five (Non-APOC), countries that were not included producing these results (18).
Although these results were based onnWHO data, IVM is not approved by the WHO as an antiviral. In August 2023, a lawyer for the American FDA stated during court proceedings that doctors have the legal authority to prescribe ivermectin off-label for COVID-19, but this did not constitute FDA approval of the drug for that use.
How does Ivermectin work?
So what's all this got to do with cancer?
This is the important part. Because once you understand how it works against parasites and insects, you will understand why it's primary action can work against so many other diseases, potentially including cancer.
Ivermectin binds to the glutamate-gated chloride channels (GluCl) found in the muscle and nerve cells of parasites. By binding to these 'gates', they stay open, and this results in an excess of chloride ions passing into the cells, reducing the healthy signaling of the cells - the parasite thus becomes paralysed and eventually dies.
How might this be relevant to cancer? Well, cancer cells rely on chloride channels more than healthy cells do. Ivermectin can completely alter the balance of chloride in a cancer cell causing the autophagy (self destruction) of cancer cells - any cancer cell, including the important Cancer Stem Cells, because, as you will see, their pathways shut down too.
Antiviral effects of Ivermectin
Just to add to the overview above, Australian researchers showed IVM could inhibit the replication of HIV-1 and dengue viruses (2); and a review of research into inhibitors of dangerous flaviviruses (West Nile Virus, Zika Virus, Yellow Fever Virus) by Chinese researchers concluded that no new antiviral drug had truly been successful but that all these viruses had a dependency on the helix lysis function of NS3 helicase and Ivermectin was proven to block this (3). For example, IVM was proven to be an inhibitor of Yellow Fever Virus (4).
Researchers have also noted a ‘multi-objective behaviour’ in Ivermectin, through its homologs, which can inhibit Covid-19 (5). It is unlikely ever to be approved as a Covid-19 treatment because to do that would mean Covid-19 vaccines could not be mandated. I think this whole covid scam has held back the development of IVM as a cancer agent, because in many countries it has even been taken off the market to allow vaccine mandates. This is depite Ivermectin being on the WHO's list of 'Essential Medicines'.
Ivermectin and cancer
Ivermectin has significant anticancer effects with multiple pathways (1). From various studies, a number of which can also be found here, these include:
- Anti-angiogenic - blocking development of blood supplies to emerging cancer tumours
- Inhibits proliferation and metastasis
- Regulates multiple signaling pathways through AMPK and PAK-1 kinase
- It inhibits HSP27 which is highly activated in many cancers
- Induces programmed cell death, apoptosis and autophagy
- Inhibits cancer stem cells
- Boosts immune system
- Reverses drug resistance across many drugs
How does it work against cancer?
This is the question we are most often asked - to recap, it is not that we don't know; it's that it works in so many ways because it can affect almost all pathways. And if you want an explanation, please polish your biochemistry degrees.
Research indicates that Ivermectin can inhibit the proliferation of cancer cells and promote apoptosis, autophagy, and pyroptosis (high inflammation cell death) in several types of cancer, including colorectal cancer, breast cancer, ovarian cancer, melanoma, and leukemia (1).
In one study on colorectal cancer (CRC), Ivermectin was found to dose-dependently inhibit the growth of certain CRC cell lines, promoting cell apoptosis and increasing Caspase-3/7 activity (8)
IVM chloride deregulation really does appear to upset a multitude of cancer pathways. For example, the AMPK pathway and the PAK1 pathway, each of which has a number of pathways with which they cross-talk. In other words, controlling these two pathways can control many others. For example, PAK1 lies at the crossroads of many paths key to tumour formation, growth, proliferation and metastasis. When highly activated, cancer is more aggressive. PAK1 inhibitors are being developed but to date, IVM seems more effective, works on more cancers and with less side-effects.
HSP27 is another such ‘controller’ pathway that Ivermectin also targets. Subsidiary pathways targeted by Ivermectin include mTOR, Akt, YAP1 and Wnt/β-catenin. Other targets include SIN3, TFE3, KPNB1, and it inhibits MDR protein and p-glycoprotein, activates chloride channels in leukaemia, increases TFE3 in melanoma and inhibits DDX23 helicase in GBM.
IVM also inhibits cancer in many ways at doses that are non-toxic to healthy cells. Ivermectin was anyway described by the FDA as one of the safest drugs ever tested!
Although a great deal of the research has been in vitro, rather than in vivo, it has been concluded that the optimal usage of Ivermectin seems to be at the same time as chemotherapy. This is because it clearly REVERSES drug resistance in cancer cells (11).
One important benefit for Ivermectin seems to be its almost extraordinary benefit with cancer stem cells where is totally disrupts and even dismantles major CSC signalling pathways such as NANOG, SOX2 and OCT4.
Breast cancer, TNBC and Ivermectin
There is research showing that IVM can target PAK1 in breast cancer (9). It also preferentially targets breast cancer stem cells in tumours over other cancer cells, also inhibiting other cancer recurrence-stimulating factors, mainly through the PAKi-STAT3 axis which regulates IL-6. City of Hope researchers showed that that P2X7 receptor presence correlated with the ability of breast cancer to grow;ivermectin could attack this pathway causing apoptosis. Ivermectin also released ATP and HMGB1, key mediators of inflammation and could thus boost the immune system preventing further cancer growth. This research took place with both breast cancer and Triple Negative Breast Cancer (9).
A team from the University of Geneva showed that IVM could block the Wnt-TCF pathway. This is hugely important because it means that Ivermectin can attack and destroy cancer stem cells (9) and this has been shown in breast cancer and lymphoma.
It also has specific research with TNBC, where it seems to reawaken protective pathways, actually making TNBC cells ‘blockable’ by Tamoxifen. Ivermectin has strong epigenetic benefits, helping to correct issues in the microenvironment of the cell. Its activities were found not to be solely cytotoxic, but it regulated the cancer cell microenvironment and, for example, promoted an immune response.
In a 2009 screening study, a farming antibiotic, Salinomycin, already known for research against breast cancer was shown to be almost 100 times stronger against stem cells than chemotherapy drugs such as Paclitaxel. In a second screening study of over 1600 chemicals, Ivermectin was identified as having the same potential as salinomycin and possibly greater. Sure enough, research against paclitaxel (16) showed that Ivermectin preferentially targeted breast cancer stem cells, while paclitaxel preferentially target normal breast cancer cells. Ivermectin also down regulated 'stemness' genes and was, of course, considerably less harmful to the body than the antibiotic or the cancer drug.
Prostate cancer and Ivermectin
IVM has been shown to inhibit prostate cancer cells, enhance the performance of Enzalutamide; and reduce drug resistance with Docetaxel - it does this by inhibiting HSP27. HSP27 is highly expressed in, and supports oncogene addiction of, many cancers (19).
Lung cancer and Ivermectin
IVM was shown to significantly inhibit the proliferation of H1299 lung cancer cells by inhibiting YAP1 activity as for gastric cancer below (6) IVM also combined with erlotinib to produce a stronger cancer cell killing effect by regulating EGFR activity. IVM also reduced the metastasis of lung cancer cells by inhibiting EMT.
Ovarian cancer and Ivermectin
Dr Hisashi Hashimto showed that Ivermectin could block the PAK1 pathway in ovarian cancer in 2009 (9). 2020 research from Chinese scientists show Ivermectin can block a number of pathways in Ovarian cancer cells (10).
Gastric, liver cancer and Ivermectin
A 2017 study showed that IVM could inhibit gastric cancer in vivo as well as in vitro (6). This was better the more the cancer depended upon the YAP1 pathway. This same effect was found in Liver cancer (7).
Colorectal cancer and Ivermectin
A 2021 study showed that IVM could inhibit Colorectal cancer cells dose-dependently, increasing Caspase-3/7 activity and causing cell apoptosis. IVM promoted both total and mitochondrial ROS production in a dose-dependent manner, so Ivermectin probably should not be used with antioxidants or off-label drugs such as NAC (8).
Pancreatic cancer and Ivermectin
A 2022 study showed that Ivermectin could suppress pancreatic cancer via mitochondrial dysfunction and that it was a very good double act alongside Gemcitabine with this cancer (14). In vivo subject groups showed a significant gain in pancreatic suppression where both were used over Gemcitabine alone. The ivermectin-gemcitabine combination inhibits cell proliferation via G1 arrest of the cell cycle, as evidenced by down-regulated cyclin D1 expression through mTOR/STAT3 signaling pathway. In addition, ivermectin-gemcitabine induces apoptosis by ROS generation and reduction of mitochondrial membrane potential (MMP), and blocking mitophagy.
Ivermectin reduces drug resistance
Apart from the above work with Docetaxel (adriamycin), Chinese researchers in Beijing showed that Ivermectin could counter drug resistance in solid tumours and leukaemia in vivo. Other studies showed effect with Taxol (9). We have a separate review on Ivermectin reducing chemo-resistance HERE.
Ivermectin dose in cancer
The standard dose in humans to knock out insects seems to be 2 mg per 10 kg of body weight. It is taken every 2 weeks as a preventative agent. Some use of the drug as an antiviral suggested the same dose everyday for 5 days. In a study with Leukemia, the same dose was used every 3 days (the half-life of Ivermectin is approximately 36 hours. In other studies it was used twice per week (12). In one study involving a child with AML, it was used daily at a triple dose level for 6 months with no reported side effects (13).
Be very careful. No one an point to cancer research stating the actual dose.
***** The 3-in-1 anti-cancer Protocol - Ivermectin, Mebendazole and Fenbendazole
Chris Woollams writes, "I am increasingly asked about combining Ivermectin with the anthelmintic drugs Fenbendazole and/or Mebendazole. This question is quite popular in younger people with Turbo cancer, and especially in older patients with recurrent Prostate cancer, Colorectal cancer and Lung cancer where the existing drugs offer little hope.
I have written a Blog specifically on this subject. You can read it HERE. I call it the '3-in-one protocol' using Fenbendazole, Mebendazole and Ivermectin. Everything I cover is based on research. I am not a Doctor. The 3-in-1 protocol came from a blog I wrote some years ago. Interestingly, some 15 US Doctors coincidentally reviewed and concurred with the elements in it. I provide details links and doses to support this protocol which deals with not just killing cancer cells but the mitochondrial stem cell connection".
Overall - Ivermectin and cancer
To repeat, there are no human clinical trials as yet and only a little in vivo work with cancer. Most of the work has been done in vitro.But clearly the potential is there, and not just in one anti-cancer route.
Ivermectin is not approved by the WHO as an anti-cancer drug.
IVM alters the chloride ion load in cancer cells effectively poisoning them, and simultaneously affects many pathways, including important ‘controller’ pathways.
It seems to improve drug performance and restrict and reverse drug resistance.
It has very few side-effects, being approved as 'a very safe drug'; overdosing may cause temporary eyesight issues, but these correct when you stop taking the drug.
There is one large 2021 research study from China that backs up all of my research above. It even lists the benefits by cancer type (1)
Go to: How to build an off-label drug programme - explained simply
*****
References
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Ivermectin, a potential anticancer drug derived from an antiparasitic drug; Mingyang Tang, Xiaodong Hu et al; Pharmacol Res; 2021 Jan; 163: 105207;
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Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus; Wagstaff K.M., Sivakumaran H., Heaton S.M., Harrich D., Jans D.A. Biochem J. 2012;443(3):851–856.
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Flavivirus: From Structure to Therapeutics Development; Rong Zhao, Meiyue Wang, Jing Cao, Jing Shen, Xin Zhou, Deping Wang, and Jimin Cao; Life (Basel) 2021 Jul; 11(7): 615.
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Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug; Mastrangelo E., Pezzullo M., De Burghgraeve T., Kaptein S., Pastorino B., Dallmeier K., de Lamballerie X., Neyts J., Hanson A.M., Frick D.N., Bolognesi M., Milani M. J Antimicrob Chemother. 2012;67(8):1884–1894.
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Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach; Lenin González-Paz, María Laura Hurtado-León, et al; Biophys Chem; 2021 Nov; 278: 106677.
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Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer; Nambara S., Masuda T et al; Oncotarget. 2017;8(64):107666–107677.
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Dysregulated YAP1/TAZ and TGF-beta signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice; Nishio M., Sugimachi K.et al; Proc Natl Acad Sci 2016;113(1):71–80.
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Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth; Shican Zhou, Hang Wu et al; Front Pharmacol, 2021 Aug 13;12:717529
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Parasite Killer Ivermectin stops cancer drug resistance
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Anti-parasite drug ivermectin can suppress ovarian cancer by regulating lncRNA-EIF4A3-mRNA axes; EPMA Journal; 2020 May 28;11(2):289-309.
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Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway; Lu Jiang et al; J Exp Clin Cancer Res 38, 265 (2019).
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Ivermectin and cancer - https://www.cancertreatmentsresearch.com/ivermectin-in-oncology/
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Continuous high-dose ivermectin appears to be safe in patients with acute myelogenous leukemia - https://www.tandfonline.com/doi/abs/10.1080/10428194.2020.1786559?journalCode=ilal20
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Abstract 2320: Ivermectin suppresses pancreatic cancer via mitochondria dysfunction; Daeun Lee et al; Cancer Res (2022) 82 (12_Supplement): 2320.
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FENBENDAZOLE in Stage 4 Cancers - the 2021 Stanford University Case Series - https://www.scitechnol.com/peer-review/fenbendazole-enhancing-antitumor-effect-a-case-series-2Kms.php?article_id=14307
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Ivermectin as an inhibitor of cancer stem like cells; Dominguez-Gomez et al; Mol Med Rep. 2018 Feb;17(2):3397-3403.
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Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal? David A Jans, Kylie M Wagstaff; Cells 2020, 9(9), 2100
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COVID-19: The Ivermectin African Enigma; Guerrero Rodrigo et al; Dec 2020 Columbia Medica
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Ivermectin inhibits HSP27 and potentiates efficacy of oncogene targeting in tumor models; Lucia Nappi et al; J Clin Invest. 2019 Dec 17;130(2):699–714
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