Repositioning of Antiparasitic Drugs for Tumor Treatment

Abstract

Drug repositioning is a strategy for identifying new antitumor drugs; this strategy allows existing and approved clinical drugs to be innovatively repurposed to treat tumors. Based on the similarities between parasitic diseases and cancer, recent studies aimed to investigate the efficacy of existing antiparasitic drugs in cancer. In this review, we selected two antihelminthic drugs (macrolides and benzimidazoles) and two antiprotozoal drugs (artemisinin and its derivatives, and quinolines) and summarized the research progresses made to date on the role of these drugs in cancer. Overall, these drugs regulate tumor growth via multiple targets, pathways, and modes of action. These antiparasitic drugs are good candidates for comprehensive, in-depth analyses of tumor occurrence and development. In-depth studies may improve the current tumor diagnoses and treatment regimens. However, for clinical application, current investigations are still insufficient, warranting more comprehensive analyses.

Plasmodium Circumsporozoite Protein Enhances the Efficacy of Gefitinib in Lung Adenocarcinoma Cells by Inhibiting Autophagy via Proteasomal Degradation of LC3B

“…Although some studies have shown these autophagy inhibitors to have promising effects in patients with intractable disease, side effects such as retinopathy and gastrointestinal problems due to agents such as hydroxychloroquine and chloroquine are an issue, and the appropriate indications for these drugs are not yet determined (Deng et al, 2019;Mulcahy and Thorburn, 2020;Uberall et al, 2019). An increasing number of studies have found that attenuated parasites (Zhou et al, 2019), blood-stage malarial parasites (Liu et al, 2017), anti-parasitic agents (Li et al, 2021;Lin et al, 2016;Vatsveen et al, 2018), and parasite proteins (Lopez et al, 2010;Ramirez-Toloza et al, 2020) had anti-tumor activity in various tumor models. These reports point to the possibility of identifying anti-tumor strategies from the perspective of parasites.…”

Plasmodium circumsporozoite protein enhances the efficacy of gefitinib in lung adenocarcinoma cells by inhibiting autophagy via proteasomal degradation of LC3B

“…Although some studies have shown these autophagy inhibitors to have promising effects in patients with intractable disease, side effects such as retinopathy and gastrointestinal problems due to agents such as hydroxychloroquine and chloroquine are an issue, and the appropriate indications for these drugs are not yet determined [16,22,23]. An increasing number of studies have found that attenuated parasites [24], blood-stage malarial parasites [25], anti-parasitic agents [26][27][28], and parasite proteins [29,30] had anti-tumor activity in various tumor models. These reports point to the possibility of identifying anti-tumor strategies from the perspective of parasites.…”

Low-Dose Albendazole Inhibits Epithelial-Mesenchymal Transition of Melanoma Cells by Enhancing Phosphorylated GSK-3β/Tyr216 Accumulation

“…Therefore, inhibiting metastasis progression is the main focus of melanoma treatment [ 31 ]. There is increasing evidence that benzimidazole can be used as a source of antitumor agents as a repositioned drug for cancer therapeutics [ 22 ]. As the most well-studied antiparasitic agent, ABZ has already been validated in a few tumor models [ 22 ].…”

“…There is increasing evidence that benzimidazole can be used as a source of antitumor agents as a repositioned drug for cancer therapeutics [ 22 ]. As the most well-studied antiparasitic agent, ABZ has already been validated in a few tumor models [ 22 ]. However, no reports are available regarding the effect of ABZ on the EMT process of melanoma.…”

“…Recently, drug repositioning has become an increasingly attractive option for medical treatments due to the pharmacokinetics and safety of existing drugs, which can reduce the difficulty and risk of clinical trials to a certain extent [ 21 , 22 ]; in addition, this strategy has economic advantages compared to complete new drug development [ 23 ]. One example is albendazole (ABZ), a kind of benzimidazole derivative and antiparasitic drug with known antitumor properties that can be repositioned as an anticancer drug [ 22 , 24 ]. Despite preexisting researches regarding that ABZ may have an antimelanoma effect by inhibiting proliferation [ 25 ] or promoting apoptosis [ 26 ], it is still unknown whether ABZ can also exhibit inhibitory effects against the metastasis of melanoma.…”