Repurposing antipsychotics of the diphenylbutylpiperidine class for cancer therapy

Area of Science:

• Oncology
• Pharmacology
• Drug Repurposing

Background:

• High throughput compound screening enables drug repurposing for novel cancer treatments.
• FDA-approved antipsychotics (fluspirilene, penfluridol, pimozide) treat schizophrenia by inhibiting dopamine D2 receptors and calcium channels.
• Observed lower cancer incidence in schizophrenia patients suggests potential anti-cancer properties of these drugs.

Purpose of the Study:

• To investigate the potential of FDA-approved antipsychotic drugs as anti-cancer agents.
• To explore the mechanisms by which these antipsychotics inhibit cancer cell proliferation and metastasis.
• To assess the synergistic effects of antipsychotics with existing chemotherapy agents.

Main Methods:

• Review of existing literature on antipsychotic drugs and their effects on various cancer cell lines (melanoma, lung, breast, pancreatic, glioma, prostate).
• Analysis of in vitro and in vivo studies detailing mechanisms of action, including apoptosis, metastasis suppression, and signaling pathways.
• Examination of pre-clinical data on drug combinations with chemotherapeutic agents.

Main Results:

• Antipsychotics demonstrated inhibition of proliferation in multiple cancer types.
• Mechanisms include induction of apoptosis, suppression of metastasis via pathways like p53, STAT3/5, and wnt/β-catenin signaling.
• Penfluridol and pimozide showed synergistic effects with chemotherapies like dasatinib, temozolomide, and cisplatin.
• Cytotoxic activity appears selective for dividing cells.

Conclusions:

• FDA-approved antipsychotics (fluspirilene, penfluridol, pimozide) show significant promise as anti-cancer agents.
• Their established safety profile and novel mechanisms warrant further investigation for cancer therapy.
• Drug repurposing of these antipsychotics offers a viable strategy for developing new cancer treatments.