Abstract

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.

Original languageEnglish (US)
Pages (from-to)111-126
Number of pages16
JournalJournal of Pharmacology and Experimental Therapeutics
Volume370
Issue number1
DOIs
StatePublished - Jan 1 2019

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Dopamine D2 Receptors
Pharmacology
Neoplasms
Ligands
Drug Therapy
Dopamine Agents
Autophagy
Lipid Metabolism
Parkinson Disease
Schizophrenia
Animal Models
Cell Culture Techniques
Apoptosis
Growth
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Cancer and the dopamine D2 receptor: A pharmacological perspective",
abstract = "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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Cancer and the dopamine D2 receptor : A pharmacological perspective. / Weissenrieder, Jillian S.; Neighbors, Jeffrey; Mailman, Richard; Hohl, Raymond.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 370, No. 1, 01.01.2019, p. 111-126.

Research output: Contribution to journalReview article

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