TY - JOUR
T1 - Cancer and the dopamine D2 receptor
T2 - A pharmacological perspective
AU - Weissenrieder, Jillian S.
AU - Neighbors, Jeffrey D.
AU - Mailman, Richard B.
AU - Hohl, Raymond J.
N1 - Funding Information:
This work was funded by the Penn State Cancer Institute, the Pritchard Distinguished Graduate Fellowship, and the National Cancer Institute (T32CA060395-21A1). The authors declare no conflicts of interest in this work.
Funding Information:
This work was supported by Public Health grants, the Penn State Cancer Institute, the Pritchard Distinguished Graduate Fellowship (Penn State College of Medicine, Hershey, PA), and the National Institutes of Health National Cancer Institute [2T32CA060395-21A1]. https://doi.org/10.1124/jpet.119.256818.
Publisher Copyright:
© 2019 by The American Society for Pharmacology and Experimental Therapeutics.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1124/jpet.119.256818
DO - 10.1124/jpet.119.256818
M3 - Review article
C2 - 31000578
AN - SCOPUS:85067371985
SN - 0022-3565
VL - 370
SP - 111
EP - 126
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -