From neuropsychiatric use to oncology: Repurposing antipsychotic drugs for cancer treatment.

Cancer remains a leading cause of mortality worldwide, and the clinical utility of conventional chemotherapeutic agents is often limited by severe systemic toxicity and the high attrition rate of novel drug candidates. Consequently, drug repurposing has emerged as an efficient strategy to identify new anticancer therapies using agents with established safety profiles. Growing epidemiological and preclinical evidence suggests that several antipsychotic drugs exhibit anticancer properties, with an inverse association reported between antipsychotic use and cancer incidence. This review systematically evaluates the anticancer potential of selected antipsychotic agents, with particular emphasis on their ability to enhance therapeutic efficacy and overcome drug resistance. A PRISMA-guided literature analysis was conducted to assess reported anticancer activities and underlying mechanisms. Antipsychotics such as chlorpromazine, haloperidol, iloperidone, and risperidone have demonstrated notable activity, primarily against colon, breast, lung, and brain cancers, while evidence in myeloma, lymphoma, and melanoma remains limited. Notably, several agents exhibit synergistic effects when combined with standard chemotherapeutics, including doxorubicin and temozolomide, and may improve sensitivity to chemotherapy and radiotherapy. However, approximately 80% of available studies are confined to in vitro models, highlighting the need for robust in vivo and clinical investigations to validate their translational potential.