The Testing Evidence for Using Ivermectin for Treating Osteosarcoma in Dogs

Executive Summary

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

Introduction

This article provides an overview covering the evidence for Ivermectin versus Osteosarcoma 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.

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Cancer Type 15: Osteosarcoma in Dogs

The following quote is from the article Repurposing Ivermectin to augment chemotherapy’s efficacy in osteosarcoma.

Ivermectin, an anti-protozoal drug, has been shown to have anti-cancer activity. This work investigated the potential of repurposing ivermectin to augment chemotherapy’s efficacy in osteosarcoma.

Ivermectin was effective and acted synergistically with doxorubicin in osteosarcoma cells regardless of cellular origin and genetic profiling. This was achieved through suppressing inhibiting growth and migration, and inducing caspase-dependent apoptosis. Ivermectin also significantly inhibited osteosarcoma growth in vivo and its combination with doxorubicin resulted in much greater efficacy than doxorubicin alone. Importantly, the effective dose of ivermectin was clinically feasible and did not cause significant toxicity in mice. Mechanistical analysis showed that ivermectin induced oxidative stress and damage, and mitochondrial dysfunction.

This is very frequently how Ivermectin has been proven effective against other cancers as well.

Proliferation, migration and apoptosis assays were performed in ivermectin-treated osteosarcoma cells. Combination studies were performed. Osteosarcoma xenograft mouse model was established to investigate the in vivo efficacy of ivermectin. Intracellular reactive oxygen species (ROS) and mitochondrial superoxide, membrane potential, ATP, 8-OHdG level, protein carbonylation and lipid peroxidation were determined after ivermectin treatment.

Ivermectin was effective and acted synergistically with doxorubicin in osteosarcoma cells regardless of cellular origin and genetic profiling. This was achieved through suppressing inhibiting growth and migration, and inducing caspase-dependent apoptosis. Ivermectin also significantly inhibited osteosarcoma growth in vivo and its combination with doxorubicin resulted in much greater efficacy than doxorubicin alone.

Doxorubicin is a chemotherapy drug. Again, it is very common for studies to show the benefits of using Ivermectin along with a chemotherapy drug.

Importantly, the effective dose of ivermectin was clinically feasible and did not cause significant toxicity in mice.

This is also quite typical. Ivermectin has very low toxicity.

Mechanistical analysis showed that ivermectin induced oxidative stress and damage, and mitochondrial dysfunction.

That is — in the cancer cells. Ivermectin disables cancer cells from multiple different mechanisms.

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.