Emetine and Its Derivatives as Anticancer Agents Targeting the PI3K/AKT/mTOR Pathway: A Narrative Review of Mechanisms, Pharmacology, and Clinical Insights

Abstract

Emetine (EMT), a naturally occurring tetrahydroisoquinoline alkaloid, shows diverse biological actions, including anticancer effects. Despite existing studies, the role of EMT derivatives in cancer, particularly in relation to the PI3K/AKT/mTOR signalling pathway, remains largely underexplored. This review explores the potential of EMT in targeting PI3K/AKT/mTOR molecular pathways across different cancer types. Data were collected from reliable and well-established sources, including PubMed, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Findings showed that EMT derivatives suppress PI3K-AKT-mTOR pathway activity in multiple cancers such as liver, gastric, acute myeloid leukaemia (AML), and brain, with IC₅₀ values ranging from 0.0244 to 1 μM. Beyond its anticancer activity, EMT showed broad pharmacological relevance, including antiviral, antiparasitic, and contraceptive activities. Preclinical assessments suggest preferential cytotoxicity toward cancer cells at low concentrations; however, known dose-dependent adverse effects, including cardiotoxicity and emetic responses at higher doses, necessitate careful dose optimization before clinical translation. Clinical evidence remains insufficient, and EMT should be considered a preclinically active compound warranting further rigorous translational investigation.