Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System

Abstract

Tumors of the digestive system, when combined together, account for more new cases and deaths per year than tumors arising in any other system of the body and their incidence continues to increase. Despite major efforts aimed at discovering and validating novel and effective drugs against these malignancies, the process of developing such drugs remains lengthy and costly, with high attrition rates. Drug repositioning (also known as drug repurposing), that is, the process of finding new uses for approved drugs, has been gaining popularity in oncological drug development as it provides the opportunity to expedite promising anti-cancer agents into clinical trials. Among the drugs considered for repurposing in oncology, compounds belonging to some classes of anthelmintics—a group of agents acting against infections caused by parasitic worms (helminths) that colonize the mammalian intestine—have shown pronounced anti-tumor activities and attracted particular attention due to their ability to target key oncogenic signal transduction pathways. In this review, we summarize and discuss the available experimental and clinical evidence about the use of anthelmintic drugs for the treatment of cancers of the digestive system.

New Trends for Antimalarial Drugs: Synergism between Antineoplastics and Antimalarials on Breast Cancer Cells

“…Since different breast cancer cell lines are metabolically different, have specific phenotypic characteristics and genotypic status, and different drug resistance patterns, further research should be made in other breast cancer cells, such as MDA-MB-231 and SUM159 cells (triple negative). Based on previous studies [36], we believe antimalarials may interfere in important oncogenic pathways such as Wnt/β-catenin, STAT3, NF-kB, and in mitochondria metabolism, leading to the formation of ROS, which sensitizes cancer cells and enhances antineoplastic drugs' activity; however, deeper mechanistic studies are recommended for further evaluation of the anticancer mechanisms underlying these combinations. These combinations should also be investigated for another types of cancer, such as pancreatic, colorectal, etc.…”

“…Antimalarial drugs have been shown to be potentially useful in the treatment of cancer [32][33][34][35]. The consideration of such drugs as possible anticancer agents relies on their ability to interfere with important oncogenic pathways, such as Wnt/β-catenin, STAT3, and NF-kB along with the emerging role of mitochondria in mediating the anti-tumor effects of antimalarials [36]. Among them, chloroquine, primaquine, and mefloquine particularly have been investigated in the treatment of numerous types of cancers, both alone and in combination with chemotherapy [37][38][39].…”

Crystal Structures of New Ivermectin Pseudopolymorphs

“…While at nanomolar concentrations it is effective mostly against nematodes, at higher concentrations, multiple new targets were identified [4,5]. Activity against various types of cancer has been reported [6][7][8][9]. IVM is an approved drug for treatment of rosacea due to its antiparasitic properties complemented by anti-inflammatory activity [10][11][12].…”

Anthelmintics for drug repurposing: Opportunities and challenges

“…Currently, the development of a new drug takes 10–15 years, and the success rate is negligible (approximately 2%). As the cost of clinical trials has recently increased, the number of new drugs, approved by Food and Drug Administration (FDA) has been decreased ( Laudisi et al, 2020 , Scannell et al, 2012 ). Between 2004 and 2012, on average 2–3 billion US dollars were spent for a pharmaceutical clinical trial, and considering the inflation, this value would be higher now ( Sertkaya, Wong, Jessup, & Beleche, 2016 ).…”