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.
Highlights
Cancer represents a major public health and economic problem and is a leading cause of death worldwide
Niclosamide (0.4, 2 and 10 μMol/L) was reported to inhibit the Wnt/β-catenin signaling pathway, whose aberrant activation occurs in approximately 80% of sporadic colorectal cancer (CRC) [65], and proliferation of the human CRC cell lines HCT-116, HT-29 and Caco2, regardless of mutations in the key regulator adenomatous polyposis coli (APC) [34]
pyrvinium pamoate (PP) inhibited the migration of HCT-116 cells in vitro and delayed liver metastases formation in a xenograft model, wherein nude mice were injected with HCT-116 cells in the portal vein and treated with PP (1 mg/kg) [57]
Summary
Cancer represents a major public health and economic problem and is a leading cause of death worldwide. Inhibition of cell growth and invasion of a human malignant cell line derived from a primary gastric tumor, whether used alone or in combination 5-FU. Anti-proliferative effects on SW480, SW620, HCT8 and Caco cells, especially when used in combination with paclitaxel. Anti-proliferative effect on SW480, SW620, HCT8, and Caco cell lines, in combination with paclitaxel. Such effect was associated with cyclin B1 and cyclin D1 down-regulation. Inhibition of the Wnt/β-catenin signaling pathway in the human CRC cell lines HCT-116, HT-29 and Caco by down-regulation of Dishevelled-2. Anti-cancer activity on CRC cells via the impairment of Wnt/β-catenin signaling pathway [47]. Synergistic anti-cancer effect on HCT-116 and SW620 cell lines in combination with 5-FU.
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