Ivermectin and cancer

stereomatch | 13 points | Jan 23 2021 20:59:57

Ivermectin and cancer

Found this interesting testimonial on ivermectin and improvement in responsiveness to cancer treatments:

https://youtu.be/0eiznbOFuwI Ivermectin for Cancer

She is saying that adding ivermectin improved response to cancer treatments greatly.

I was aware of it's usefulness in cancer treatment - because was researching for someone who has a family member undergoing chemotherapy.

https://youtu.be/NOpiMasSvSE

Whiteboard Doctor reviews the recent results on Ivermectin

At 18:45 minute mark reviews study out of Bangladesh where they gave Ivermectin to cancer patients suffering from covid19 with good results

https://www.nature.com/articles/ja201711

15 February 2017

Review Article

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

Globally, breast cancer is the most common cancer among women but treatment options are few. Ivermectin suppresses breast cancer by activating cytostatic autophagy, disrupting cellular signaling in the process, probably by reducing PAK1 expression. Ivermectin-induced cytostatic autophagy also leads to suppression of tumor growth in breast cancer xenografts, causing researchers to believe there is scope for using ivermectin to inhibit breast cancer cell proliferation and that the drug is a potential treatment for breast cancer. Cancer stem cells are a key factor in cancer cells developing resistance to chemotherapies and these results indicate that a combination of chemotherapy agents plus ivermectin could potentially target and kill cancer stem cells, a paramount goal in overcoming cancer.

Also see a previous post:

https://www.reddit.com/r/ivermectin/comments/kqmvor Ivermectin, a potential anticancer drug derived from an antiparasitic drug (China 2020-09-21)

EDIT: (March 1, 2021)

https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1251-7 Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway

Lu Jiang, Pan Wang, Ying-Jian Sun & Yi-Jun Wu

Journal of Experimental & Clinical Cancer Research

Published: 18 June 2019

Results

Our results indicated that ivermectin at its very low dose, which did not induce obvious cytotoxicity, drastically reversed the resistance of the tumor cells to the chemotherapeutic drugs both in vitro and in vivo. Mechanistically, ivermectin reversed the resistance mainly by reducing the expression of P-glycoprotein (P-gp) via inhibiting the epidermal growth factor receptor (EGFR), not by directly inhibiting P-gp activity. Ivermectin bound with the extracellular domain of EGFR, which inhibited the activation of EGFR and its downstream signaling cascade ERK/Akt/NF-κB. The inhibition of the transcriptional factor NF-κB led to the reduced P-gp transcription.

Conclusions

These findings demonstrated that ivermectin significantly enhanced the anti-cancer efficacy of chemotherapeutic drugs to tumor cells, especially in the drug-resistant cells. Thus, ivermectin, a FDA-approved antiparasitic drug, could potentially be used in combination with chemotherapeutic agents to treat cancers and in particular, the drug-resistant cancers.

https://www.biorxiv.org/content/10.1101/2020.08.21.261511v1.full Ivermectin converts cold tumors hot and synergies with immune checkpoint blockade for treatment of breast cancer

Dobrin Draganov, Zhen Han, Nitasha Bennett, Darrell J. Irvine, Peter P. Lee

Posted August 24, 2020.

doi: https://doi.org/10.1101/2020.08.21.261511

Abstract

We show that treatment with the FDA-approved anti-parasitic drug ivermectin induces immunogenic cancer cell death (ICD) and robust T cell infiltration into breast tumors. As an allosteric modulator of the ATP/P2×4/P2×7 axis which operates in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations including myeloid cells and Tregs, resulting in enhanced Teff/Tregs ratio. While neither agent alone showed efficacy in vivo, combination therapy with ivermectin and checkpoint inhibitor anti-PD1 antibody achieved synergy in limiting tumor growth (p=0.03) and promoted complete responses (p<0.01), also leading to immunity against contralateral re-challenge with demonstrated anti-tumor immune responses. Going beyond primary tumors, this combination achieved significant reduction in relapse after neoadjuvant (p=0.03) and adjuvant treatment (p<0.001), and potential cures in metastatic disease (p<0.001). Statistical modeling confirmed bona fide synergistic activity in both the adjuvant (p=0.007) and metastatic settings (p<0.001). Ivermectin has dual immunomodulatory and ICD-inducing effects in breast cancer, converting ‘cold’ tumors ‘hot’, thus represents a rational mechanistic partner with checkpoint blockade.

Checkpoint blockade (1, 2) has emerged as a revolutionary approach that harnesses a patient’s own immune system to treat cancer. However, checkpoint inhibitors as single agents are only effective in a subset of patients and cancer types (2). Recent studies suggest that efficacy of checkpoint inhibitors is primarily limited to cancers already infiltrated by T cells – often termed ‘hot’ tumors. In contrast, ‘cold’ tumors have little to no T cell infiltration and generally do not respond to checkpoint blockade. Early clinical studies with checkpoint blockade therapy in breast cancer have focused on triple negative breast cancer (TNBC), because this subtype has a higher mutational load and is thought to be more ‘immunogenic’ (3). Even so, anti-PD1/PDL1 antibodies have produced clinical responses in only a small subset (15-20%) of TNBC patients (4). As such, there is considerable interest in identifying drugs capable of priming breast tumors (turning ‘cold’ tumors ‘hot’) to synergize with checkpoint blockade.

A recently described phenomenon, termed immunogenic cell death (ICD) (5, 6), is a form of cell death that induces an immune response from the host. ICD is distinguished from classical apoptosis and other non-immunogenic or tolerogenic forms of cell death by several hallmarks, including release of ATP and HMGB1 and surface exposure of calreticulin (5-7). In cancer patients, ICD-based anti-tumor immune responses are linked to beneficial outcomes produced by some conventional chemotherapeutic agents (8-11). For example, efficacy of anthracyclines in breast cancer (12-14) and oxaliplatin in colorectal cancer (15) correlates with post-treatment increases in the ratio of cytotoxic CD8+ T lymphocytes to FoxP3+ regulatory T cells within the tumor. In contrast, poor responses to chemotherapy in solid tumors are associated with lymphopenia (16). Thus, ICD-inducing chemotherapy appears to work in conjunction with the host immune system to achieve efficacy. However, chemotherapy is a double-edged sword: it can suppress as well as stimulate immune cells. An agent that induces ICD of cancer cells without suppressing immune function would be ideal for combination with checkpoint blockade. Seeking such an agent among FDA-approved drugs, our group found that the anti-parasitic agent ivermectin promotes ICD in breast cancer cells(17). Among our previous findings was evidence that ivermectin, an anti-parasitic drug used worldwide since 1975, modulates the P2×4/P2×7 purinergic pathway, suggesting that ivermectin may further harness tumors’ intrinsic high extracellular levels of ATP for anti-cancer activity. Of note, P2×4/P2×7 receptors are widely expressed on various immune subpopulations, suggesting that ivermectin might also have direct immunomodulatory effects.

EDIT: this video describes use of another deworming drug - mebendazole:

https://www.youtube.com/watch?v=2-YrZMIK37U

This could change the way cancer is treated | The Economist

Jun 1, 2019

The Economist

1.81M subscribers

A combination of drugs, including aspirin and statins, are being tested to treat cancer and other illnesses. There is mounting clinical evidence that the "repurposing" of existing drugs could offer effective new treatments. Read more here: https://econ.st/2WgHlpz Click here to subscribe to The Economist on YouTube: https://econ.st/2xvTKdy Right now we’d like to take a few moments to tell you all about aspirin. Did you know that aspirin may help treat cancer as well as headaches. The pain’s gone, so tension’s gone. It’s not the only drug being used to treat an illness that it wasn’t originally intended for. But for some people, using old drugs for new treatments or “repurposing” can be the difference between life and death. I still can’t find the appropriate words to describe how horrible it is to have to tell your own parents that you’ll be dead before them. Melanie Kennedy, mother of two young boys was diagnosed with breast cancer in 2013. It soon spread to her liver. She was given five years to live. If you have an incurable cancer you want to explore every option. Nobody wants to leave their children early and nobody wants to die young. Determined to see her children grow up she began to search for experimental treatments to help combat the disease. I did a lot of research into what else was out there because I wanted to outlive the five years. I looked into quite a few different options which is how I found out about repurposed drugs. Through a private-health clinic Melanie began a course of treatment using repurposed drugs while continuing conventional chemotherapy with the NHS. The clinic recommended she take an antibiotic called doxycycline, metformin, usually used to treat type-2 diabetes, a statin, or cholesterol-lowering drug, and mebendazole, a worming agent. All these drugs were designed for other purposes but may have anti-cancer properties. In simple terms repurposing drugs is taking an existing drug that has been licensed for a particular therapeutic indication or a medical condition and seeking to use it in a different clinical setting. A very good example is that of aspirin which actually was initially used as a painkiller when it was first licensed. Nowadays we predominantly use it as a blood thinner but actually there are clinical trials in progress looking at its role in an anti-cancer setting. So why aren’t more drugs repurposed? When a new drug is brought to market it is protected by a patent giving the company that developed it exclusive rights to sell it. This stops copycat drugs being sold by competitors allowing the developer to make a profit. But many existing drugs that could be repurposed are no longer covered by patents so companies have less incentive to pay the cost of testing them for new conditions. And there’s another stumbling block. Doctors are reluctant to prescribe a drug to treat an illness that it wasn’t designed for. We’re very loth to use medications outside of the particular reasons that they’re licensed for use. And that’s because if there are any issues when patients then take those drugs the doctor is ultimately responsible. To make sure Melanie isn’t having problems with the experimental drugs she must have regular checkups. Hi Mel, lovely to see you. Do you want to give me a little bit of an overview? How have things been since we last spoke to you? – Great, I’ve had another scan. After a two-year course of chemotherapy along with repurposed drugs her scans are showing no new evidence of disease. When I got the news that my liver was clear. I didn’t believe him. I made him turn the computer monitor around and I read it for myself. Doctors can’t say with certainty that her dramatic improvement was caused by the repurposed drugs. For that the trial she’s part of must be completed. But there’s a lot of clinical evidence to suggest that there’s a huge untapped medicine cabinet of generic drugs that could help treat cancer. And many other conditions including motor neurone disease and schizophrenia. There are many benefits of repurposing medications. I suppose the main one is in terms of both time and money. Most new medications cost over $2bn to bring through the whole clinical-trial process and actually license them for use in clinical practice. That takes a long time and is expensive for drug companies and for the NHS. Drug repurposing is cheaper than developing new medicines because the drug has already been tested for safety which itself is hugely expensive. Melanie believes this trial has saved her life. But for more trials like this to take place governments will need to change the incentives for pharmaceutical companies and solve the patent problem.

EDIT: 2021-04-11 - some more references:

https://link.springer.com/article/10.1007/s13167-020-00209-y Anti-parasite drug ivermectin can suppress ovarian cancer by regulating lncRNA-EIF4A3-mRNA axes 28 May 2020

Discussion Anti-parasite drug ivermectin used a broad spectrum of disease models. Recently, ivermectin, as a promising anticancer agent, showed remarkable ability to block tumor progression. For example, the oncogenic kinase PAK1 was somehow essential for tumorigenesis and growth in more than 70% human cancers, including cervical, breast, thyroid, prostate, pancreatic, lung, colon, gastric, hepatoma, melanoma, and glioma cancers. Study showed that ivermectin suppressed the growth of multiple human OC cell lines in vitro and in a xenograft mouse model by inactivating PAK1 [37]. Moreover, there were almost no adverse effects for ivermectin treatment. Ivermectin exerts selective toxicity and has protective effect on normal cells [38]. In fact, the study shows that IC50 (30.12 mol/L) of “normal” breast epithelial cell line MCF-10A was much higher than breast cancer cells (< 20 mol/L), such as cancer cells MCF-7 (9.30 mol/L), MDA-MB-231 (10.48 mol/L), MDA-MB-468 (16.20 mol/L), MDA-MB-361 (13.44 mol/L), MDA-MB-435 (15.10 mol/L), and HS578T (17.29 mol/L) [9]. It clearly demonstrates that in vitro and in vivo antitumor activities of ivermectin can be achieved at relatively low concentration range, while such a concentration range is safe for healthy and parasitic patients based on human pharmacokinetic studies, which was beneficial to rapid move of ivermectin into clinical trials for cancer patients. Ivermectin was also used as chemotherapeutic sensitizer of, for example, platinum that was common chemotherapeutics for OC. Antiestrogens, including tamoxifen and fulvestrant, could be the effective treatment for OC in cases of platinum resistant. Ivermectin sensitized OC cells to fulvestrant and tamoxifen by blocking HE4/importin-4 nuclear accumulation [39]. Additionally, the synergy was also observed between ivermectin and BCR-ABL TKIs in acute myeloid leukemia, and the ivermectin can induce cell death and chloride-dependent membrane hyperpolarization in acute myeloid leukemia cells [12]. Considering risks and costs, drug redirecting, as the identification of novel usages for existing drugs, it would be possible to monitor pharmacokinetic and pharmacodynamics profiles of ivermectin in vitro and in vivo [8]. ...

https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-019-2026-2 Ivermectin inhibits canine mammary tumor growth by regulating cell cycle progression and WNT signaling August 2, 2019

https://cancerres.aacrjournals.org/content/76/15/4457 Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer August 2016

https://www.intechopen.com/online-first/the-anti-cancer-effects-of-anti-parasite-drug-ivermectin-in-ovarian-cancer The Anti-Cancer Effects of Anti-Parasite Drug Ivermectin in Ovarian Cancer By Xianquan Zhan and Na Li Submitted: September 23rd 2020 Reviewed: December 19th 2020 Published: January 13th 2021

https://www.spandidos-publications.com/10.3892/mmr.2017.8231 Ivermectin as an inhibitor of cancer stem‑like cells December 8, 2017

Inhibitory effects of ivermectin and paclitaxel in stem cell enriched MDA-MB-231 cells The CD44+/CD24− subpopulation of MDA-MB-231 cells has been previously reported to possess stem/progenitor cell properties, and this subpopulation in patients with breast cancer exclusively retains the ability to form novel tumors in a non-obese diabetic-severe compromised immunodeficiency mouse xenograft model ... In conclusion, results from the present study demonstrated that ivermectin preferentially targeted the stem cell population in MDA-MB-231 human breast cancer cells. Ivermectin has been demonstrated to be safe, following treatment of millions of patients with onchocerciasis and other parasitic diseases, which makes it a strong candidate for further studies investigating its potential use as a repurposed drug for cancer therapy.

https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15195 Ivermectin suppresses tumour growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma March 31, 2020

DISCUSSION In summary, our study demonstrated that ivermectin effectively suppressed ESCC cell growth, migration and invasion through blocking the PAK1 signalling. We also found that ivermectin displayed significant antitumour effects on tumorigenesis and lung metastasis in xenografted mouse models, and improved the sensitivity to the first‐line chemotherapeutic drugs including CDDP or 5‐FU. Given that ivermectin has been approved by FDA for treatment of human diseases, our data warrant a clinical trial of ivermectin for treatment of ESCC patients, even those with metastasis or chemotherapeutic resistance.