Therapeutic and Imaging Applications of Dopamine Receptors in Breast Cancer
Technical Report,01 Sep 2014,31 Aug 2015
University of Cincinnati Cincinnati United States
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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 D4and 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.