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Multifaceted effect of chlorpromazine in cancer: implications for cancer treatment

Pareesa Kamgar-Dayhoff and Tinatin I. Brelidze _

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Oncotarget. 2021; 12:1406-1426. https://doi.org/10.18632/oncotarget.28010

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Abstract

Pareesa Kamgar-Dayhoff1 and Tinatin I. Brelidze1

1 Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, D.C., USA

Correspondence to:

Tinatin I. Brelidze,email: tib5@georgetown.edu

Keywords: chlorpromazine; repurposing

Received: April 23, 2021     Accepted: June 14, 2021     Published: July 06, 2021

Copyright: © 2021 Kamgar-Dayhoff and Brelidze. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Since its discovery in 1951, chlorpromazine (CPZ) has been one of the most widely used antipsychotic medications for treating schizophrenia and other psychiatric disorders. In addition to its antipsychotic effect, many studies in the last several decades have found that CPZ has a potent antitumorigenic effect. These studies have shown that CPZ affects a number of molecular oncogenic targets through multiple pathways, including the regulation of cell cycle, cancer growth and metastasis, chemo-resistance and stemness of cancer cells. Here we review studies on molecular mechanisms of CPZ’s action on key proteins involved in cancer, including p53, YAP, Ras protein, ion channels, and MAPKs. We discuss common and overlapping signaling pathways of CPZ’s action, its cancer-type specificity, antitumorigenic effects of CPZ reported in animal models and population studies on the rate of cancer in psychiatric patients. We also discuss the potential benefits and limitations of repurposing CPZ for cancer treatment.


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