Ivermectin in Oncology: Is Ivermectin a Cancer Solution?

By Dr. Frank Yap, MD - September 23, 2024

Ivermectin is a widely used antiparasitic drug that's listed on the World Health Organization's essential medicines list1 and approved by the U.S. Food and Drug Administration. In low- and middle-income countries, ivermectin is commonly used to treat parasitic diseases including onchocerciasis (river blindness), strongyloidiasis and other diseases caused by soil-transmitted helminthiasis, or parasitic worms.2

The drug is also used to treat scabies and lice. It's estimated that the total number of ivermectin doses distributed is equal to one-third of the world's population and, as such, "ivermectin at the usual doses (0.2–0.4 mg/kg) is considered extremely safe for use in humans." (3)

Related: The Surprising Potential of Ivermectin Against Cancer: Dr. Kathleen Ruddy

Ivermectin's Powerful Antitumor Effects

Ivermectin has notable antitumor effects, which include inhibiting proliferation, metastasis and angiogenic activity in cancer cells (6). It appears to inhibit tumor cells by regulating multiple signaling pathways, which researchers explained in the Pharmacological Research journal, "suggests that ivermectin may be an anticancer drug with great potential." (7)

Their graphic, below, shows the multiple ways that ivermectin may target cancer, including inducing apoptosis and autophagy while also inhibiting tumor stem cells and reversing multidrug resistance. They stated that ivermectin "exerts the optimal effect when used in combination with other chemotherapy drugs." (8)

Pharmacol Res. 2021 Jan; 163: 105207

Many may not be aware that scientists Satoshi ōmura and William C. Campbell won the Nobel Prize in Physiology or Medicine in 2015 for their discovery of ivermectin.9 The medicine is used to treat not only parasitic diseases like malaria but also shows promise for treating asthma and neurological diseases, in addition to cancer.

Along with direct cytotoxic effects, it's believed that ivermectin regulates the tumor microenvironment, mediating immunogenic cell death — another reason for its promise as an anticancer agent.10 Research suggests the drug may be useful for the following cancers:11

Breast cancer — The proliferation of multiple breast cancer cell lines was significantly reduced following treatment with ivermectin.
Digestive system cancer — Ivermectin significantly inhibited the proliferation of gastric cancer cells in vivo and in vitro. The drug also inhibited colorectal cancer cell lines and inhibited the development of hepatocellular carcinoma (liver cancer).
Urinary system cancer — Ivermectin significantly inhibited the proliferation of five renal (kidney) cell carcinoma lines without affecting normal kidney cells. It also had an inhibitory effect on prostate cancer cells.
Hematological cancer — In one study, ivermectin killed leukemia cells at low concentrations while leaving normal hematopoietic cells unharmed.
Reproductive system cancer — Ivermectin inhibited the proliferation of ovarian cancer cell lines and enhanced the efficacy of the conventional chemotherapy drug cisplatin, improving the treatment of epithelial ovarian cancer.
Brain glioma — Ivermectin inhibited the proliferation of human glioblastoma cells in a dose-dependent manner.
Respiratory system cancer — Ivermectin inhibited the development of nasopharyngeal carcinoma in mice, using doses that were not toxic to immune cells known as thymocytes. Ivermectin also significantly inhibited the proliferation of lung cancer cells and may reduce the metastasis of lung cancer cells.
Melanoma — When melanoma cells were treated with ivermectin, their activity was effectively inhibited.

Ivermectin in Oncology – The Basic Science

In laboratory, Ivermectin has been shown to be able to kill cancer cells of many types, such as

Breast Cancer (Ref.1, Ref.2, Ref.3)
Ovarian Cancer (Ref.1, Ref.2)
Prostate Cancer (Ref.)
Colorectal Cancer (Ref,)
Brain Cancer (Ref.1, Ref.2, Ref.3, Ref.4)
Renal Cancer (Ref.)
Leukemia (Ref.)
AML (Ref.)
Hepatocellular carcinoma (Ref.)
Lung Cancer (Ref.1, Ref.2)
and many others.

However, many substances have been shown to kill cancer in laboratory. So why would Ivermectin be more relevant?

Ivermectin, stands out in my view because it acts as a strong ionophore and up-regulates chloride channels (Ref.).

Indeed, Ivermectin is known to increase the activity of glutamate-chloride ion channel, increasing the influx of chloride ions inside the cells, and consequently blocking signal transmission between neurons and muscles. This is the main mechanism which is responsible for its antiparasitic effects. At a higher concentration, ivermectin also stimulates chloride channels in mammals.

While as we will see below Ivermectin works through multiple anti cancer mechanisms, I believe its interference with ion dynamics across cellular membrane is the most important property responsible for the anti cancer effects of Ivermectin (Ref.). This is because, the over activity of cancer cells vs normal cells requires an intense movement of ions outside-in and inside-out of ions such as Potassium, Chloride, etc.

During the past years, I have discussed why this ion dynamics is so important and in that context I addressed outstanding Ionophores such as Salinomycin or Ion transporters inhibitors such as Bufalin. Other ion transporter inhibitors known to have outstanding anti cancer properties are e.g. Oubain, Oleander, Digoxins, also known as Cardiac Glycosides.

Cardiac Glycosides, act on the K/Na exchange while Salinomycin mainly on Potassium. That is different compared to Chloride that is the initial target of Ivermectin. However, no matter which “string you pull” you end up affecting the dynamics of many other ions. So when you act on Chloride, you will end up also affecting Potassium and the other way around.

Actually, this is what electro-magnetic fields are also doing and this is why they have potential to affect the development of tumors, as they mess up with the ion dynamics. In turn, interference with ion dynamics can have impact on e.g. intracellular pH and as a result impact functionality of various enzymes, and at a more general level interference with major intracellular pathways and mechanisms.

As a reminder, Salinomycin remains the most effective anti cancer drug I have seen, and I believe Ivermectin is not far from that in terms of potential. However, because of its accessibility, well known safety, and ease of implementation Ivermectin may be even more relevant.

Coming back to Chloride that is affected by Ivermectin, it may be interesting to remember that Chlorotoxin found in scorpion venom (see my post on scorpion venom) (Ref.) can also inhibit chloride channels. This leads to the opposite outcome in terms of Chlorine ion dynamics but the result is still killing the cancer cell (Ref.). This is a similar story with that of pro-oxidants and anti-oxidants treatment strategies in oncology. No matter which one you pick it will be effective against cancer as long as it is done in a coherent manner, so that the treatments used they are either pro- or anti-oxidants. Same here with Chlorine intracellular accumulation (by Ivermectin) or depletion by scorpion venom. We shoudl chouse either one, or the other but not both at the same time.

Nevertheless, academic research has indicated that Ivermectin can address many more mechanism that can lead to tumor suppression. Whether all or some of those mechanisms have at the base its ionophore activity remains to be seen. Nevertheless, the list of anti cancer mechanisms related to Ivermectin is outstanding:

Can trigger “Immunogenic Cancer Cell Death”. This is a form of cancer cell death that “wakes up” the immune system and therefore initiates an immune response. As a result, it has been proposed that Ivermectin coudl be a great combination with forms of immuno therapy such as checkpoint inhibitors. (Ref.)
Downregulates glutathione S-transferases (GSTs) and vascular endothelial growth factor (VEGF) (Ref.)
Potentiated activity of anti–androgen receptor and anti-EGFR drugs (Ref.)
Inhibited cancer stem‑like cells (CSC) (Ref.)
Inhibits angiogenesis (Ref.)
Inhibition of metastasis (Ref.)
WNT pathway inhibitor (Ref.1)
Increased reactive oxygen species generation that was functionally important for ivermectin-induced cell death (Ref.)
Microtubule inhibitor (Ref.)
Multi Drug Resistance Pumps inhibitor (Ref.)
At a higher dose, Ivermectin can inactivate the protein kinase PAK1 and blocks the PAK1 dependent growth – PAK1 is critical for cytoskeleton reorganization and nuclear signalling. PAK-1 kinase is required for the growth of more than 70% of human cancers (Ref.) This activity is similar to Caffeic Acid from Propolis.

This amazing list of activity explains why Ivermectin has such as large anti cancer potential.

Ivermectin in Oncology – First Results in Humans

Source 1: When searching for new treatment options in oncology, in order to identify the value and not look at the noise, its best to look for two important aspects: clear science and at least a first indication that the treatment option has been applied in humans with some success. In other words, we look for good knowledge and signal of activity.

While the science is strong when it comes to Ivermectin, until the recent years we had no case report published in the scientific literature that would support the expectations from science.

Fortunately, very recently a paper has been published where Ivermectin has been used as part of a drug cocktail in patients with no effective treatment options (Ref.). In this paper, 3 cases have been discussed and in each of the cases benefits have been observed after just adding a low dose of Ivermectin:

Case 1: A 69-year-old female diagnosed with invasive breast cancer underwent left breast partial mastectomy, but bone metastases and pleural dissemination appeared. After conventional treatments have become less effective, and intolerable side effects appeared, her doctors decided to switch to a combo of dichloroacetate, omeprazole, and tamoxifen. This helped to relieved her symptoms (bone pain, shortness of breath, and general fatigue) instantly but not completely. After adding a tablet of 12 mg ivermectin per day the pleural effusion has been stabilized and the tumor marker CEA started decline from 12.9 to 7.3, and cancer antigen 15-3 (CA15-3), from 302.3 to 229.4 in three months. (Ref.) Note: my understanding is that the Ivermectin has only been used here one time per week.

Case 2: A 54-year-old male was diagnosed with right femur osteosarcoma. While on conventional treatments, lung lymph node metastases and pleural dissemination appeared. At that point he could not walk out of his house himself because of shortness of breath and severe pain. His doctors, decided to switch to a combo of dichloroacetate, omeprazole, tamoxifen and ivermectin at a dose of 12 mg 2x/week, on Day 1 and Day 4. After only one cycle, all the symptoms were relieved dramatically, and he could go to the clinic on foot by himself. (Ref.)

Case 3: A 54-year-old male was diagnosed with right lung adenocarcinoma. While the chemo was initially effective, gradually it became less effective and metastases (bone and brain) appeared. His doctors, decided to switch to a combo of dichloroacetate, omeprazole, and ivermectin at a dose of 12 mg one time per week. However, his symptoms (cough, shortness of breath, pain, and appetite loss) did not improve. After increasing the dose of Ivermectin to 12 mg 2x/week, the symptoms were relieved. (Ref.)

While the results presented in this report may not be impressive, they demonstrate that Ivermectin has the potential to add good value to the life of cancer patients.

The question is what can we do to maximize its value. One aspect that becomes imidiatly clear after reading the report above, is that the dose and the ferquency of administration used was very conservative. The other point is that delivering Ivermectin more targeted to the tumor via intravenous administration or rectal administration could maximize the effects of Ivermectin.

Source 2: After digging more into the literature, I found another very important report, on the use of high dose Ivermectin in paediatric patients with refractory AML. (Ref.). In this case, a 1 mg/kg dose has been used daily for six months with no major side effects, while bennefits have been also observed.

Source 3: In addition to the above, Dr. Simon Yu states “If you have Medically Unexplainable Symptoms (MUS) or cancer, you may consider trying Ivermectin, deworming medication.”. (Ref.) In another post by Dr. Simon Yu he stated “I have experienced some dramatic responses for medically unexplained symptoms and some cancer cases.”. He also stated “monthly de-worming for medically unexplained symptoms or for cancer patients might be a better solution”. (Ref.) Dr. Simon Yu also liked to combine Ivermectin with Praziquantel another of his favorited anti parasitic drugs.

Ivermectin Dosage for Cancer

According to the scientific literature, Ivermectin has been administered so far orally, intravenously and rectally (Ref.).

Nebulized Ivermectin has also been proposed for direct delivery to the lungs and this could very much make sense for patients with tumors at the lungs (Ref.). In this case the authors have proposed solving Ivermectin in ethanol as described in the article. This is not a new concept to be discussed on this Blog as we have discussed similar concept for e.g. 3BP (Ref.).

The most suitable daily dose of Ivermectin as a repurposed drug in oncology has not been well defined yet. Therefore, before getting to a conclusion, we need to look at multiple refernces to identify the dose that could be high enough and safe enough to be used.

a first reference point when it comes to the use of Ivermectin, is dr. Simon Yu. To my understanding some of his slides are suggesting that a common anti parasitic dose in his view is 12 mg 3-4x/daily for 10 up to 30 days (Ref.) I would assume this is for a person of 70kg, that woudl indicate a 0.7 mg/kg daily dose.
on the other hand, the study referenced above, showing positive results in oncology, based on a daily dose of 12 mg, given one to two times per week (Ref.)
indeed, a recent systematic review, including a meta-analysis, has shown that adverse effects following single-dose treatment with up to 0.8 mg/kg of Ivermectin occur without significant differences of frequency or intensity to those at regular currently approved doses (Ref.)
here is a paper published in The Lancet in 1994, where patients have been treated with Ivermectin doses up to 1.6mg/kg given as subsequent injections at weekly or biweekly intervals. ” No clinical adverse effects were noted in any of the patients, including the one who received ivermectin for 12 weeks. In fact, many reported improved sleep, less depression, and better bowel and bladder function during the trial.” (Ref.)
a recent review on Ivermectin safety, also states that there is “no difference in the severity of the adverse events between standard (up to 0.4 mg/kg) and higher doses of ivermectin. Organ system involvement only showed an increase in ocular events in the higher-dose group in one trial for the treatment of onchocerciasis, all of them transient and mild to moderate in intensity.” (Ref.)
another extensive study in humans using an Ivermectin dose of 0.6 mg/kg/day for 5 days, reported on both the safety and possible efficacy of high dose ivermectin as an anti viral (Ref1, Ref.2.)
finally, Ivermectin has been used at a dose as high as 1 mg/kg in pedriatic patinet wih AML, for six months, with no major side effect (Ref.)

Based on the above, I would consider using

a dose of 0.6 mg to 1 mg/kg/day,
taken once a day (single dose),
with food

If active cancer, I would take it in one of the following ways:

5 days ON and 2 days OFF, or
20 days ON and 10 days OFF, or
if highly active cancer, I would take it continuously, at least in the first months

In non active cancer, I would take it in the following way: 10 days ON and 20 days OFF, repeat this during the second month so that there are two cycles performed, one after each other. I would do this, 2x/year.

I like the idea to combine it with one more anti parasitic such as Praziquantel, as often done by Dr. Simon Yu.

NOTE:

The doses discussed above are coming from references following its use in humans, in some cases for as long as 6 months in pediatric patients. That sounds as a good safety profile at that dose.

Nevertheless, it must be made clear that the statement on the safety of the drug at normal dose comes from a very large set of data related to its use in humans, while the safety as stated at higher doses comes on very limited set of data. Therefore, I would never go to the target dose immediately when starting Ivermectin. Instead, if the target dose would be 1 mg/kg/day, I would start first with 0.1 mg/kg/day, and move step by step towards the 1 mg/kg/day during a few/several weeks. This approach will help to identify potential side effcets. And that, done with the support of a medical doctor.

Is Liposomal Delivery a Game Changer?

The development of an injectable form of ivermectin, or liposomal ivermectin, could help overcome some of its limitations regarding solubility and open its use to a broader range of cancers. The cancer immunotherapy treatment pembrolizumab, for instance, is approved to treat PD-L1-positive, triple-negative breast cancer, which accounts for only about 20% of cases.

As an immune checkpoint inhibitor, it works best in so-called "hot" tumors, which are already infiltrated by T cells. If ivermectin could be injected into the tumor, inducing T-cell infiltration into the area and inducing immunogenic cancer cell death, it's possible that it could turn a "cold" tumor into a "hot" one, thereby making it more effectively treated.16

Biotech company Mountain Valley MD has developed a liposomal delivery system for ivermectin that they believe could dramatically widen its treatment potential. In an interview with Medical Update Online, Dennis Hancock, Mountain Valley MD president and CEO, explained:17

"So the business value proposition really simply is, we take the best-selling and best-acting drugs and expand their ability to be used on … more types of cancer on a broader spectrum. So you still need the cancer drug and what our Ivectosol does is it enables it to be used in a broader universe …

What's really exciting about the work that Mountain Valley MD is doing is we're enabling drugs that have already been proven in their efficacy and safety to do better and do more faster — so we're not asking people to 'wait five years and see'…"

Most of the research involving ivermectin for cancer to date involves oral or in-vitro administration. Mountain Valley MD is conducting preclinical trials using liposomal ivermectin for metastatic melanoma, non-small cell lung cancer, triple-negative breast cancer and possibly bladder cancers. They also have plans to produce liposomal ivermectin for use in human trials.18 In a news release, Mike Farber, director of life sciences at Mountain Valley MD, stated:19

"The extensive research supporting the drug ivermectin as effective in the inhibition of proliferation, metastasis, and angiogenic activity in a variety of cancers, and as an initiator of immunogenic cell death, is overwhelming. Imagine what is possible when you have the world's only human injectable form of ivermectin that can be directly injected into a tumor or provided through more bio-available forms such as intravenously.

We believe this will be groundbreaking research with near-immediate application to be able to proceed directly to human trials based on the safety and efficacy of ivermectin."

*Disclaimer

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

References

Sources:

https://articles.mercola.com/sites/articles/archive/2022/05/12/ivermectin-antitumor-effects.aspx

https://www.cancertreatmentsresearch.com/ivermectin-in-oncology/

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