%0 Journal Article %A Jillian S Weissenrieder %A Jeffrey D Neighbors %A Richard B Mailman %A Raymond J Hohl %T Cancer and the dopamine D2 receptor: a pharmacological perspective %D 2019 %R 10.1124/jpet.119.256818 %J Journal of Pharmacology and Experimental Therapeutics %P jpet.119.256818 %X The dopamine D2 receptor (D2R) family is upregulated in many cancers, and tied to stemness, while cancer risk may correlate with dopamine-related disorders such as schizophrenia and Parkinson's disease. D2R antagonists also have anticancer efficacy in cell culture and animal models where they reduce tumor growth, induce autophagy, affect lipid metabolism, and cause apoptosis, among other effects. This has led to the hypothesis that D2R ligands are a novel approach to cancer chemotherapy, a particularly appealing concept because of the large number of approved and experimental drugs of this class. We review the current state of the literature, and the evidence for and against this hypothesis. When the existing literature is evaluated from a pharmacological context, one of the striking findings is that the concentrations needed for cytotoxic effects of D2R antagonists are orders of magnitude higher than their affinity for this receptor. Although additional definitive studies will provide further clarity, our hypothesis is that targeting D2-like dopamine receptors will not yield useful ligands for cancer chemotherapy.SIGNIFICANCE STATEMENT Here we review the literature on the anticancer effects of dopamine D2-receptor antagonists such as the common anti-pyschotic drugs. During the course of this review we have come to the conclusion that the effects of these drugs in the context of cancers such as glioblastoma, is unlikely to be mediated by the D2-receptor and is instead due to other off target effects of these agents. %U https://jpet.aspetjournals.org/content/jpet/early/2019/04/24/jpet.119.256818.full.pdf