>>15242588 (pb)

MOAR IVERMECTIN BRAIN CANCER WONDERMENT

"Targeting tumor hypoxia and mitochondrial metabolism with anti-parasitic drugs to improve radiation response in high-grade gliomas"

Abstract

High-grade gliomas (HGGs), including glioblastoma and diffuse intrinsic pontine glioma, are amongst the most fatal brain tumors. These tumors are associated with a dismal prognosis with a median survival of less than 15 months. Radiotherapy has been the mainstay of treatment of HGGs for decades; however, pronounced radioresistance is the major obstacle towards the successful radiotherapy treatment. Herein, tumor hypoxia is identified as a significant contributor to the radioresistance of HGGs as oxygenation is critical for the effectiveness of radiotherapy. Hypoxia plays a fundamental role in the aggressive and resistant phenotype of all solid tumors, including HGGs, by upregulating hypoxia-inducible factors (HIFs) which stimulate vital enzymes responsible for cancer survival under hypoxic stress. Since current attempts to target tumor hypoxia focus on reducing oxygen demand of tumor cells by decreasing oxygen consumption rate (OCR), an attractive strategy to achieve this is by inhibiting mitochondrial oxidative phosphorylation, as it could decrease OCR, and increase oxygenation, and could therefore improve the radiation response in HGGs. This approach would also help in eradicating the radioresistant glioma stem cells (GSCs) as these predominantly rely on mitochondrial metabolism for survival. Here, we highlight the potential for repurposing anti-parasitic drugs to abolish tumor hypoxia and induce apoptosis of GSCs. Current literature provides compelling evidence that these drugs (atovaquone, ivermectin, proguanil, mefloquine, and quinacrine) could be effective against cancers by mechanisms including inhibition of mitochondrial metabolism and tumor hypoxia and inducing DNA damage. Therefore, combining these drugs with radiotherapy could potentially enhance the radiosensitivity of HGGs. The reported efficacy of these agents against glioblastomas and their ability to penetrate the blood-brain barrier provides further support towards promising results and clinical translation of these agents for HGGs treatment.

https://jeccr.biomedcentral.com/articles/10.1186/s13046-020-01724-6

>>15242727

Excitement Begins Over Ivermectin's Anti-Cancer 'Repurposing' Against Brain

Lung and Breast Cancers

"Drug Repositioning for Cancer Therapy Based on Large-Scale Drug-Induced Transcriptional Signatures"

Haeseung Lee,Seungmin Kang,Wankyu Kim

Published: March 8, 2016

https://doi.org/10.1371/journal.pone.0150460

Abstract

An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug’s mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. EIGHT OF THE FOUTEEN DRUGS SHOWED SIGNIFICANT ANTI-PROLIFERATIVE ACTIVITY AGAINST GLIOBLASTOMA, I.E., (((IVERMECTIN))), trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150460

>>15242785

MOAR EARLIER IVERMECTIN BRIAN

"Anthelmintic drug ivermectin inhibits angiogenesis, growth and survival of glioblastoma through inducing mitochondrial dysfunction and oxidative stress"

October 2016 Biochemical and Biophysical Research Communications 480(3)

DOI:10.1016/j.bbrc.2016.10.064

Abstract

Glioblastoma is one of the most vascular brain tumour and highly resistant to current therapy. Targeting both glioblastoma cells and angiogenesis may present an effective therapeutic strategy for glioblastoma. In our work, we show that an anthelmintic drug, ivermectin, is active against glioblastoma cells in vitro and in vivo, and also targets angiogenesis. Ivermectin significantly inhibits growth and anchorage-independent colony formation in U87 and T98G glioblastoma cells. It induces apoptosis in these cells through a caspase-dependent manner. Ivermectin significantly suppresses the growth of two independent glioblastoma xenograft mouse models. In addition, ivermectin effectively targets angiogenesis through inhibiting capillary network formation, proliferation and survival in human brain microvascular endothelial cell (HBMEC). Mechanistically, ivermectin decreases mitochondrial respiration, membrane potential, ATP levels and increases mitochondrial superoxide in U87, T98G and HBMEC cells exposed to ivermectin. The inhibitory effects ivermectin are significantly reversed in mitochondria-deficient cells or cells treated with antioxidants, further confirming that ivermectin acts through mitochondrial respiration inhibition and induction of oxidative stress. Importantly, we show that ivermectin suppresses phosphorylation of Akt, mTOR and ribosomal S6 in glioblastoma and HBMEC cells, suggesting its inhibitory role in deactivating Akt/mTOR pathway. Altogether, our work demonstrates that ivermectin is a useful addition to the treatment armamentarium for glioblastoma. Our work also highlights the therapeutic value of targeting mitochondrial metabolism in glioblastoma.

https://www.researchgate.net/publication/309308531_Anthelmintic_drug_ivermectin_inhibits_angiogenesis_growth_and_survival_of_glioblastoma_through_inducing_mitochondrial_dysfunction_and_oxidative_stress

>>15242806

NEXT IVERMECTIN POSITIVE CANCER

STUDY HAS BEEN SCRUBBED

Please archive previous studies.

>>15242824

Earliest Ivermectin Anti-Cancer Study Yet

Research Article20 August 2014

OPEN ACCESS

"The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer"

Alice Melotti

Christophe Mas

Monika Kuciak

Aiala Lorente-Trigos

Isabel Borges

Ariel Ruiz i Altaba

https://www.embopress.org/doi/full/10.15252/emmm.201404084

>>15242838

"Anti-parasitic drug discovered in 1975 could be ‘game-changer’ in fight against cancer"

An anti-parasitic drug discovered in 1975 could be a "game-changer" in the fight against cancer, scientists have claimed.

23:33, Sun, Aug 29, 2021 | UPDATED: 23:40, Sun, Aug 29, 2021

Since its discovery by the Kitasato Institute in Tokyo, Ivermectin has been used to treat some of the world's most persistent tropical diseases including onchocerciasis, helminthiases, and scabies. The microorganism which is native to Japanese soil has been hailed as a wonder drug by scientists but was constantly let down by poor solubility - its ability to be turned into a liquid.

Despite hopes being raised about its cancer fighting abilities, difficulties to inject it into patients rendered effective research into this impossible for decades.

Now scientists at Canada-based pharmaceutical company Mountain Valley MD claim to have found a way to dissolve the drug into a substance they are calling Ivectosol.

They have said this has opened up the possibility of using the drug in combination with existing checkpoint inhibitors to target cancer cells more effectively.

Checkpoint inhibitors are a class of drugs that work to help the human immune system detect and eradicate cancerous cells.

https://www.express.co.uk/life-style/health/1483711/cancer-news-drug-Mountain-Valley-Ivermectin-latest