Cancer and the Dopamine D₂ Receptor: A Pharmacological Perspective

The dopamine D₂ receptor (D₂R) family is upregulated in many cancers and tied to stemness. Reduced cancer risk has been correlated with disorders such as schizophrenia and Parkinson's disease, in which dopaminergic drugs are used. D₂R antagonists are reported to have anticancer efficacy in cell culture and animal models where they have reduced tumor growth, induced autophagy, affected lipid metabolism, and caused apoptosis, among other effects. This has led to several hypotheses, the most prevalent being that D₂R ligands may be a novel approach to cancer chemotherapy. This hypothesis is appealing because of the large number of approved and experimental drugs of this class that could be repurposed. 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 may only yield useful ligands for cancer chemotherapy in rare cases.