The Testing Evidence for Using Ivermectin for Treating Malignant Melanoma in Dogs

Executive Summary

• This article covers the evidence I could find for Ivermectin as a treatment for Malignant Melanoma in Dogs.

Introduction

In this article, I cover the effectiveness of Ivermectin versus Malignant Melanoma in Dogs.

In many articles on this site, such as the article How Ivermectin Is Useful for Treating Cancer we covered the evidence for the benefits of Ivermectin for cancer. However, the topic of which specific cancers Ivermectin has been proven effective is a constant source of questions.

There are a lot of quotes in this article, but I have a short one for each cancer type. The article uses the term “IVM” to mean Ivermectin.

About the Brightwork Research Treatment Database

We have a subscription website that provides people with everything they need to know about using Ivermectin for several diseases. Cancer is just one of our most researched areas. To see more see the below article indexes. 

Article Indexes

• Open this link to see just one example Ivermectin article index.
• Open this link to see the full article index. 

We have the most research on Ivermectin and Ivermectin for cancer and are completely independent. However, we have to charge subscribers to stay independent. We have free articles that expose readers to our research and writing -- however most of our content is behind a paywall. 

Cancer Type #6: Malignant Melanoma in Dogs

Melanoma is the most common malignant skin tumor with a high mortality rate. Drugs targeting BRAF mutations such as vemurafenib, dabrafenib and PD-1 monoclonal antibodies, including pembrolizumab and nivolumab have greatly improved the prognosis of melanoma. Gallardo treated melanoma cells with IVM and found that it could effectively inhibit melanoma activity. Interestingly, IVM could also show activity against BRAF wild-type melanoma cells, and its combination with dapafinib could significantly increase antitumor activity. Additionally, it has been confirmed that PAK1 is the key target of IVM that mediates its anti-melanoma activity, and IVM can also significantly reduce the lung metastasis of melanoma in animal experiments. Deng found that IVM could activate the nuclear translocation of TFE3 and induce autophagy-dependent cell death by dephosphorylation of TFE3 (Ser321) in SK-MEL-28 melanoma cells. However, NAC reversed the effect of IVM, which indicated that IVM increased TFE3-dependent autophagy through the ROS signaling pathway.

This metanalysis study was published on the NIH or National Institutes of Health website. However, it was funded by Indian science institutes.

Regarding the dosage and sourcing of Ivermectin, see the article On the Topic of Ivermectin Dosage and Sourcing.

Testing Evidence for Ivermectin

The following quotes are from the article Ivermectin, a potential anticancer drug derived from an antiparasitic drug.

Impact #1: Inhibiting Proliferation of Tumor Cells

Recently, ivermectin has been reported to inhibit the proliferation of several tumor cells by regulating multiple signaling pathways.

The Ivermectin blocking of PAK1 proteins, aka activated kinase, is a reason for this.

The instrumentality of PAK1 in cancer growth is explained in the following quotation from the article Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations.

In human ovarian cancer and NF2 tumor cell lines, high-dose ivermectin inactivates protein kinase PAK1 and blocks PAK1-dependent growth.

PAK proteins are essential for cytoskeletal reorganization and nuclear signaling, PAK1 being implicated in tumor genesis while inhibiting PAK1 signals induces tumor cell apoptosis (cell death).

PAK1 is essential for the growth of more than 70% of all human cancers, including breast, prostate, pancreatic, colon, gastric, lung, cervical and thyroid cancers, as well as hepatoma, glioma, melanoma, multiple myeloma and for neurofibromatosis tumors.

PAK1 becomes hyperactive in cancer cells for reasons that are not yet understood.

Ivermectin can be viewed as a PAK1 restrictor or modulator (I say modulator as PAK1 is present in normal healthy cells, but an overage of PAK is a prime cause of cancer.)

This means that Ivermectin interferes with a precursor to cancer. This modulating influence on PAK is another reason Ivermectin is effective against many types of cancer.

PAK1 is implicated in multiple cancers if found in the quotation from the article Effect of P21-activated kinase 1 (PAK-1) inhibition on cancer cell growth, migration, and invasion.

Previous studies showed that PAK-1 mediated the growth of prostate PC-3 cell tumor xenografts in athymic nude mice as well as the transforming growth factor-β (TGFβ)-induced prostate cancer cell epithelial-mesenchymal transition (EMT). These studies suggested that PAK-1 plays a major role in prostate cancer progression and is a potential target for prostate cancer therapy. PAK-1 has also been suggested to be involved in the early stages of breast cancer and may partially participate in the mechanisms mediating the transformation of mammary epithelial cells into mesenchymal malignant cells.

Hyperactive PAK1 and Cancer

This is explained in the quotation from P21 Activated Kinase-1 (Pak1) Promotes Prostate Tumor Growth and Microinvasion via Inhibition of Transforming Growth Factor β Expression and Enhanced Matrix Metalloproteinase 9 Secretion.

Even though Pak1 has been identified in normal prostatic epithelial cells and cancer cells, its specific role in the development of prostate cancer remains unclear. We report here that highly invasive prostate cancer cells express significantly higher levels of Pak1 protein compared with non-invasive prostate cancer cells. Furthermore, prostate tumor tissues and prostate cancer metastasized to lungs showed a higher expression of Pak1 compared with normal tissues.

This appears to match the experience with other cancers, but they have not performed sufficient studies to say for sure.