Therapeutic and Imaging Applications of Dopamine Receptors in Breast Cancer

Abstract

Patients with advanced breast cancer either do not respond to anti-hormonal therapy or develop resistance to chemotherapy,providing major incentives to seek novel therapies that circumvent these drawbacks. Dopamine (DA) is a catecholamine which acts as a neurotransmitter in the brain and as a hormone in the periphery. DA binds to five receptors, D2-like (D2, D3 and D4)and D1-like (D1 and D5). Our data show that D1R is overexpressed in breast carcinomas while adjacent normal breast tissue is D1R-negative. Fenoldopam, a potent D1R agonist, was highly effective in suppressing xenograft growth in mice, by increasing both apoptosis and necrosis. An imaging system for detecting D1R-expressing breast tumors has been developed,albeit it requires additional improvements. These data suggest that D1R analysis in tumor biopsies could serve as a prognostic biomarker for advanced breast cancer. Moreover, Fenoldopam, an FDA approved, selective D1R agonist which does not penetrate the brain, should be exploited as a novel therapeutic agent in patients who do not respond to standard of care therapy.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2015
Accession Number
AD1005298

Entities

People

  • Nira Ben-jonathan

Organizations

  • University of Cincinnati

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biomedical Research
  • Breast Cancer
  • Carcinoma
  • Catecholamines
  • Cell Line
  • Cells
  • Chemotherapy
  • Detection
  • Diseases And Disorders
  • Dopamine
  • Gene Expression
  • Lymph Nodes
  • Necrosis
  • Neoplasms
  • Statistical Analysis
  • Therapy

Fields of Study

  • Biology
  • Medicine

Readers

  • Breast cancer cell signaling and growth regulation.
  • Neuroscience
  • Oncology