However, in breast cancer cell experiments, it was also found that IVM could induce autophagy, and enhanced autophagy could increase the anticancer activity of IVM [37]. However, to date, no exact target for IVM action has been found. Glioblastoma is the deadliest glioma, with a median survival time of only 14-17 months [61,62]. For some older drugs that are widely used for their original indications and have clinical data and safety information, drug repositioning allows them to be developed via a cheaper and faster cycle and to be used more effectively in clinical use clinically [29]. Wang J., Xu Y., Wan H., Hu J. Gastric cancer is one of the most common malignant tumors worldwide. 15 Jan 2023 21:28:26 (1) Although a large number of research results indicate that IVM affects multiple signaling pathways in tumor cells and inhibits proliferation, IVM may cause antitumor activity in tumor cells through specific targets. Nishio M., Sugimachi K., Goto H., Wang J., Morikawa T., Miyachi Y., Takano Y., Hikasa H., Itoh T., Suzuki S.O., Kurihara H., Aishima S., Leask A., Sasaki T., Nakano T., Nishina H., Nishikawa Y., Sekido Y., Nakao K., Shin-Ya K., Mimori K., Suzuki A. Dysregulated YAP1/TAZ and TGF-beta signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice. McKerrow J.H. The inflammasome is a multimolecular complex containing pattern recognition receptor (PRR), apoptosis-associated speck-like protein containing a CARD (ASC), and pro-caspase-1. Nambaras study showed that IVM could significantly inhibit the proliferation of gastric cancer cells in vivo and in vitro and that the inhibitory effect of IVM depended on the expression of Yes-associated protein 1(YAP1)[39]. We use cookies to enhance your experience. . IVM halted the cell cycle in S phase and promoted apoptosis. It was based on a very small flawed 2002 study mentioned in a 2011 study. MDR of tumor cells is the main cause of relapses and deaths after chemotherapy [97]. Yang J.D., Hainaut P., Gores G.J., Amadou A., Plymoth A., Roberts L.R. Antoszczak M., Markowska A., Markowska J., Huczynski A. There are still some problems that need to be studied and resolved before IVM is used in the clinic. Rectal cancer. A systematic literature review and network meta-analysis of effectiveness and safety outcomes in advanced melanoma. Perspectives on the utility of moxidectin for the control of parasitic nematodes in the face of developing anthelmintic resistance. . In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in . We believe that IVM can be further developed and introduced clinically as part of new cancer treatments in the near future. After using the autophagy inhibitor bafilomycin A1 or siRNA to downregulate Beclin1, IVM-induced apoptosis was significantly enhanced, which suggested that enhanced autophagy will reduce IVM-induced apoptosis and that IVM-induced autophagy can protect tumor cells from apoptosis. Prostate cancer is a malignant tumor derived from prostate epithelial cells, and its morbidity is second only to that of lung cancer among men in Western countries [49]. Foy B.D., Alout H., Seaman J.A., Rao S., Magalhaes T., Wade M., Parikh S., Soma D.D., Sagna A.B., Fournet F., Slater H.C., Bougma R., Drabo F., Diabate A., Coulidiaty A.G.V., Rouamba N., Dabire R.K. Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial. Galluzzi L., Bravo-San Pedro J.M., Demaria S., Formenti S.C., Kroemer G. Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy. Relatively safe. Introduction. Pouliot J.F., LHeureux F., Liu Z., Prichard R.K., Georges E. Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. WASHINGTON Ivermectin, a controversial drug used commonly as a horse dewormer as well as a treatment for parasitic infections in humans, could be capable of treating COVID-19 patients and potentially ending the pandemic, some scientists claim.The team of researchers, including three U.S. government senior scientists, are calling for governments around the world to start treating . This is a randomized, doubled-blind and placebo-controlled phase II study that will evaluate the efficacy of the early use of ivermectin plus losartan in cancer patients who present with recent diagnosis of COVID-19. Old wine in new bottles: Drug repurposing in oncology. Zhang P., Zhang Y., Liu K., Liu B., Xu W., Gao J., Ding L., Tao L. Ivermectin induces cell cycle arrest and apoptosis of HeLa cells via mitochondrial pathway. Surprisingly, gemcitabine-resistant KKU214 cells showed high sensitivity to IVM, which suggested that IVM shows potential for the treatment of tumors that are resistant to conventional chemotherapy drugs. Despite the fact that these trials found ivermectin inferior to the cream it was being tested against, it still won approval due to its low cost and ease of administration. However, whether ivermectin affects CRC is still unclear. In Nappi's experiment, it was found that IVM could enhance the drug activity of the anti-androgen drug enzalutamide in the prostate cancer cell line LNCaP and reverse the resistance of the prostate cancer cell line PC3 to docetaxel [50]. In mid-2020, an ivermectin study published in the prestigious New England Journal of Medicine was retracted. Emerging Role of Circulating Tumor Cells in Gastric Cancer. Here, we systematically summarized the anticancer effect and mechanism of IVM, which is of great significance for the repositioning of IVM for cancer treatment. IVM induces different programmed cell death patterns in different tumor cells (Table 1). The study group included adult patients from 12 cities throughout Brazil, where ivermectin has been widely embraced and utilized since the early months of the pandemic. 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 . In research to screen potential targets for the treatment of ovarian cancer through the use of an shRNA library and a CRISPR/Cas9 library, the oncogene KPNB1 was detected. Finally, IVM changed the balance between apoptosis-related proteins by upregulating the protein Bax and downregulating anti-apoptotic protein Bcl-2, thereby activating caspase-9/-3 to induce apoptosis [48,53,63] (Fig. Ivermectin is approved for human . In Didier's experiments testing the effect of IVM on lymphocytic leukemia, IVM could be used as an inhibitor of P-gp to affect MDR [22]. The present study represents the first study evaluating the anticancer efficacy of ivermectin in pancreatic cancer. In a study published in the journal Oncotarget on July 6, Gregory Riggins, M.D., Ph.D., professor of neurosurgery and oncology at the Johns Hopkins University School of Medicine, and his team used two different mouse models to determine that the anti-parasitic drug mebendazole could slow or stop the growth and spread of both early and late-stage pancreatic cancer. Carneiro S.R., da Silva Lima A.A., de Fatima Silva Santos G., de Oliveira C.S.B., Almeida M.C.V., da Conceicao Nascimento Pinheiro M. Relationship between Oxidative Stress and Physical Activity in Women with Squamous Intraepithelial Lesions in a Cervical Cancer Control Program in the Brazilian Amazon. As mentioned above, the anticancer mechanism of IVM involves a wide range of signaling pathways such as Wnt/-catenin, Akt/mTOR, MAPK and other possible targets such as PAK1 and HSP27, as well as other mechanisms of action (Table 2 Diana A., Carlino F., Franzese E., Oikonomidou O., Criscitiello C., De Vita F., Ciardiello F., Orditura M. Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes. Likes. Ivermectin has powerful antitumor effects, including the inhibition of proliferation, metastasis, and angiogenic activity, in a variety of cancer cells. What this study does and does not show. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. Importantly, IVM is an established drug used for the treatment of parasitic diseases such as river blindness and elephantiasis. The Panel reviewed other clinical studies of IVM for the treatment of COVID-19. Nishio found that IVM could significantly inhibit the proliferation of H1299 lung cancer cells by inhibiting YAP1 activity [43]. Cervical cancer is one of the most common gynecological malignancies, resulting in approximately 530,000 new cases and 270,000 deaths worldwide each year. Overall, we speculate that IVM can regulate the Akt/mTOR, MAPK and other pathways that are essential for tumor cell proliferation by inhibiting PAK1 expression, which plays an anticancer role in most cancers. In addition to IVM, the current avermectin family members include selamectin, doramectin and moxidectin [[2], [3], [4], [5]] (Fig. All of the above findings indicate the potential of IVM as an autophagy activator to induce autophagy-dependent death in tumor cells. You may switch to Article in classic view. The decrease in the mitochondrial membrane potential and the cytochrome c is released from mitochondria into the cytoplasm was detected after the intervention of IVM in Hela cells [56].Therefore, we infer that IVM induces apoptosis mainly through the mitochondrial pathway. The FDA first issued a warning in April 2020 that ivermectin intended for use in animals should not be used to treat COVID-19 . Background Discovery and development of novel drugs that are capable of overcoming drug resistance in tumor cells are urgently needed clinically. Autophagy-Independent Functions of the Autophagy Machinery. Recently, ivermectin, a well-known anti-parasite drug, was reported to share the same mechanisms with them and have anti-tumor activity. The secondary objectives of the study include evaluating the following efficacy outcomes: objective response rate (ORR), progression free survival (PFS), overall survival (OS), duration of response (DOR . Ivermectin has been called a Covid "miracle" drug, championed by vaccine opponents, and recommended by health authorities in some countries. We have already mentioned that IVM plays an anticancer role in various tumors by regulating pathways closely related to cancer development. Cancer stem cells (CSCs) are a cell population similar to stem cells with characteristics of self-renewal and differentiation potential in tumor tissue [89,90]. Several studies have confirmed that IVM could reverse drug resistance by inhibiting P-gp and MDR-associated proteins [[101], [102], [103]]. Levy J.M.M., Towers C.G., Thorburn A. But the question of which cancers Ivermectin has been proven effective is a constant source of questions. Deepak K.G.K., Vempati R., Nagaraju G.P., Dasari V.R., N. S, Rao D.N., Malla R.R. The study found that patients with Covid-19 treated in hospital who "received ivermectin early reported substantial recovery" and that there was "a substantial improvement and reduction in . Following the study, the FDA released a letter out of concern warning consumers not to self-medicate with ivermectin products intended for animals. Kwak H.J., Kim Y.J., Chun K.R., Woo Y.M., Park S.J., Jeong J.A., Jo S.H., Kim T.H., Min H.S., Chae J.S., Choi E.J., Kim G., Shin S.H., Gwak H.S., Kim S.K., Hong E.K., Lee G.K., Choi K.H., Kim J.H., Yoo H., Park J.B., Lee S.H. Abstract. Existing research is sufficient to demonstrate the great potential of IVM and its prospects as a novel promising anticancer drug after additional research. Ivermectin is an anthelmintic. Ravegnini G., Sammarini G., Nannini M., Pantaleo M.A., Biasco G., Hrelia P., Angelini S. Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis. The PAK1-Stat3 Signaling Pathway Activates IL-6 Gene Transcription and Human Breast Cancer Stem Cell Formation. (4) IVM can enhance the sensitivity of chemotherapeutic drugs and reduce the production of resistance. Patel H., Yacoub N., Mishra R., White A., Long Y., Alanazi S., Garrett J.T. Gewirtz D.A. It is intended as a sharing of knowledge and information from the research and experience of Dr. Mercola and his community. Obviously, the existing results suggest that IVM-induced apoptosis and autophagy also exhibit cross talk. With the development of derivatives of the avermectin family that are more efficient and less toxic, relevant research on the anticancer mechanism of the derivatives still has great value. If you are pregnant, nursing, taking medication, or have a medical . On average, a new case is diagnosed every 18 seconds worldwide [30,31]. Pyroptosis is a type of inflammatory cell death induced by inflammasomes. Wang Y., Su J., Wang Y., Fu D., Ideozu J.E., Geng H., Cui Q., Wang C., Chen R., Yu Y., Niu Y., Yue D. The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1- NF-kappaB signaling axis. Current Advances in the Treatment of BRAF-Mutant Melanoma. Liu Y., Fang S., Sun Q., Liu B. Anthelmintic drug ivermectin inhibits angiogenesis, growth and survival of glioblastoma through inducing mitochondrial dysfunction and oxidative stress. This was related to the induction of mitochondrial dysfunction and oxidative stress. Franken M.G., Leeneman B., Gheorghe M., Uyl-de Groot C.A., Haanen J., van Baal P.H.M. IVM.YAP1 plays an oncogenic role in tumorigenesis, indicating the possibility of the use of IVM as a YAP1 inhibitor for cancer treatment . Dammann K., Khare V., Gasche C. 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