Anti-Parasitic Drugs in Cancer Therapy: Analyzing drugs like ivermectin, fenbendazole and mebendazole for their potential to disrupt cancer cell signaling or enhance chemotherapy

By Editorial Team
Anti-parasitic drugs such as ivermectin, fenbendazole, and mebendazole have shown promising potential in cancer therapy by disrupting cancer cell signaling and enhancing chemotherapy efficacy through multiple mechanisms.

Fenbendazole

Fenbendazole, a benzimidazole anthelmintic, exhibits several anti-cancer effects:

  • Microtubule disruption: Fenbendazole acts as a moderate microtubule destabilizing agent, impairing microtubule polymerization which is critical for cancer cell division46.

  • Metabolic interference: It inhibits glucose uptake by downregulating GLUT1 transporters and hexokinase II (HKII), key components of glycolysis, thereby starving cancer cells of energy and reversing drug resistance146.

  • Activation of p53 pathway: Fenbendazole induces mitochondrial translocation of p53, promoting apoptosis and cell cycle arrest at the G2/M phase124.

  • Induction of multiple cell death pathways: It triggers apoptosis, necrosis, autophagy, and ferroptosis, including in 5-fluorouracil-resistant colorectal cancer cells, suggesting utility against drug-resistant tumors12.

  • Proteasomal inhibition: Fenbendazole impairs proteasomal function, contributing to its cytotoxicity4.

  • Immunomodulation: Some studies indicate fenbendazole may alter tumor microenvironment immune activity, though in vivo effects need further clarification5.

  • Enhancement of chemotherapy: Benzimidazoles like fenbendazole have been shown to enhance the efficacy of conventional chemotherapeutics such as paclitaxel and doxorubicin, particularly in resistant cancer cells67.

Mebendazole

Mebendazole, another benzimidazole, shares similar mechanisms:

  • It disrupts microtubule dynamics, leading to cell cycle arrest and apoptosis.

  • It inhibits glucose metabolism and induces autophagic and apoptotic cancer cell death.

  • Mebendazole has shown efficacy in overcoming drug resistance and enhancing chemotherapy response in various cancer models68.

Ivermectin

Ivermectin, an antiparasitic distinct from benzimidazoles, also demonstrates anti-cancer properties:

  • It disrupts multiple cancer cell signaling pathways, including WNT-TCF, AKT/mTOR, and PAK1, leading to inhibition of proliferation and induction of apoptosis.

  • Ivermectin can reverse multidrug resistance and sensitize cancer cells to chemotherapeutic agents.

  • It also modulates the tumor microenvironment and immune response, contributing to its anti-tumor effects8.

Summary

These antiparasitic drugs disrupt cancer cell energy metabolism, interfere with cytoskeletal dynamics, activate tumor suppressor pathways, and induce multiple forms of cell death. Their ability to target resistant cancer cells and enhance chemotherapy highlights their potential as repurposed agents in cancer therapy12468. Further clinical studies are warranted to confirm efficacy and optimize combination regimens.

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