Repurposing monepantel in oncology: A conceptual mini-review of proposed mechanisms

Monepantel (MPL), an amino‑acetonitrile derivative (AAD) anthelmintic, is widely used for the treatment of nematode infections in livestock like sheep and cattle. Additionally, it has gained attention as a potential candidate for drug repurposing in oncology. While its antiparasitic action depends on nematode-specific nicotinic acetylcholine receptors, emerging evidence has revealed a distinct mechanism in mammalian cancer cells. MPL inhibits the mTOR/p70S6K signaling axis, induces autophagic responses, disrupts cell‑cycle progression, and enhances endoplasmic reticulum stress (ER-stress). Each one of these effects point to the potential of MPL benefit in cancer treatment. This mini-review integrates preclinical and early clinical findings and highlights the anticancer mechanisms linked to MPL, including its ability to cause G1 arrest, activate endoplasmic reticulum stress pathways, and enhance the efficacy of conventional chemotherapies, all while maintaining an exceptional safety profile. The sections that follow examine the mechanistic basis and translational promise of MPL as a repurposed anticancer agent.