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Cancers 2019, 11(3), 358; https://doi.org/10.3390/cancers11030358

ADRB2-Targeting Therapies for Prostate Cancer

1
Department of Cancer Biology, Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC 27157, USA
2
Department of Life Sciences, Alfaisal University, Riyadh 11533, Saudi Arabia
Received: 18 February 2019 / Revised: 7 March 2019 / Accepted: 8 March 2019 / Published: 13 March 2019
(This article belongs to the Special Issue Apoptosis in Cancer)
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Abstract

There is accumulating evidence that β-2 adrenergic receptor (ADRB2) signaling contributes to the progression and therapy resistance of prostate cancer, whereas availability of clinically tested β-blocker propranolol makes this pathway especially attractive as potential therapeutic target. Yet even in tumors with active ADRB2 signaling propranolol may be ineffective. Inhibition of apoptosis is one of the major mechanisms by which activation of ADRB2 contributes to prostate cancer pathophysiology. The signaling network that controls apoptosis in prostate tumors is highly redundant, with several signaling pathways targeting a few critical apoptosis regulatory molecules. Therefore, a comprehensive analysis of ADRB2 signaling in the context of other signaling mechanisms is necessary to identify patients who will benefit from propranolol therapy. This review discusses how information on the antiapoptotic mechanisms activated by ADRB2 can guide clinical trials of ADRB2 antagonist propranolol as potential life-extending therapy for prostate cancer. To select patients for clinical trials of propranolol three classes of biomarkers are proposed. First, biomarkers of ADRB2/cAMP-dependent protein kinase (PKA) pathway activation; second, biomarkers that inform about activation of other signaling pathways unrelated to ADRB2; third, apoptosis regulatory molecules controlled by ADRB2 signaling and other survival signaling pathways. View Full-Text
Keywords: β-2 adrenergic receptor (ADRB2); cAMP-dependent protein kinase (PKA); prostate cancer; propranolol; apoptosis; clinical trial; BCL-2-associated death promoter (BAD); myeloid cell leukemia 1 (MCL-1) β-2 adrenergic receptor (ADRB2); cAMP-dependent protein kinase (PKA); prostate cancer; propranolol; apoptosis; clinical trial; BCL-2-associated death promoter (BAD); myeloid cell leukemia 1 (MCL-1)
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Kulik, G. ADRB2-Targeting Therapies for Prostate Cancer. Cancers 2019, 11, 358.

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