Drug Design, Development and Therapy (Jun 2021)
Progress in Redirecting Antiparasitic Drugs for Cancer Treatment
Abstract
Haoyang Huang,1 Qing He,2– 5 Binghua Guo,6 Xudong Xu,7 Yinjuan Wu,2– 5 Xuerong Li2– 5 1Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Key Laboratory for Tropical Diseases Control of Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 4Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou, Guangdong, 510080, People’s Republic of China; 5CAEA Center of Excellence on Nuclear Technology Applications for Insect Control, Beijing, 100048, People’s Republic of China; 6School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 7Department of Clinical Medicine, School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Xuerong LiDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaTel +86 20 87331918Fax +86 20 87331918Email [email protected]: Drug repurposing is a feasible strategy in developing novel medications. Regarding the cancer field, scientists are continuously making efforts to redirect conventional drugs into cancer treatment. This approach aims at exploring new applications in the existing agents. Antiparasitic medications, including artemisinin derivatives (ARTs), quinine-related compounds, niclosamide, ivermectin, albendazole derivatives, nitazoxanide and pyrimethamine, have been deeply investigated and widely applied in treating various parasitic diseases for a long time. Generally, their pharmacokinetic and pharmacodynamic properties are well understood, while the side effects are roughly acceptable. Scientists noticed that some of these agents have anticancer potentials and explored the underlying mechanisms to achieve drug repurposing. Recent studies show that these agents inhibit cancer progression via multiple interesting ways, inducing ferroptosis induction, autophagy regulation, mitochondrial disturbance, immunoregulation, and metabolic disruption. In this review, we summarize the recent advancement in uncovering antiparasitic drugs’ anticancer properties from the perspective of their pharmacological targets. Instead of paying attention to the previously discovered mechanisms, we focus more on newly emerging ones that are worth noticing. While most investigations are focusing on the mechanisms of their antiparasitic effect, more in vivo exploration in clinical trials in the future is necessary. Moreover, we also paid attention to what limits the clinical application of these agents. For some of these agents like ARTs and niclosamide, drug modification, novel delivery system invention, or drug combination are strongly recommended for future exploration.Keywords: ferroptosis, autophagy, mitochondria, immunoregulation, glycolysis
