The role of androgen therapy in prostate cancer: from testosterone replacement therapy to bipolar androgen therapy

Xie, Tao; Song, Xiaolei; Wang, Chong; Wang, Jing-Quan; Chen, Zhe‐Sheng; Zhao, Shan‐Chao

doi:10.1016/j.drudis.2021.01.034

Cited by 11 publications

(11 citation statements)

References 84 publications

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“…Androgen (testosterone) is a major growth factor for PC and ADT is a standard and effective treatment for PC [ 18 ]. However, PC eventually develops resistance to ADT, undergoes NED, and emerges as treatment-resistant NEPC.…”

Section: Discussionmentioning

confidence: 99%

Sympathetic signaling facilitates progression of neuroendocrine prostate cancer

et al. 2021

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The progression of prostate cancer (PC) into neuroendocrine prostate cancer (NEPC) is a major challenge in treating PC. In NEPC, the PC cells undergo neuroendocrine differentiation (NED); however, the exact molecular mechanism that triggers NED is unknown. Peripheral nerves are recently shown to promote PC. However, their contribution to NEPC was not studied well. In this study, we explored whether sympathetic neurosignaling contributes to NED. We found that human prostate tumors from patients that later developed metastases and castration-resistant prostate cancer (CRPC), a stage preceding to NEPC, have high sympathetic innervations. Our work revealed that high concentrations of the sympathetic neurotransmitter norepinephrine (NE) induces NED-like changes in PC cells in vitro, evident by their characteristic cellular and molecular changes. The NE-mediated NED was effectively inhibited by the Adrβ2 blocker propranolol. Strikingly, propranolol along with castration also significantly inhibited the development and progression of NEPC in vivo in an orthotopic NEPC model. Altogether, our results indicate that the NE-Adrβ2 axis is a potential therapeutic intervention point for NEPC.

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Section: Discussionmentioning

confidence: 99%

Sympathetic signaling facilitates progression of neuroendocrine prostate cancer

et al. 2021

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“…AR expression. Aberrant changes in AR render it sensitive to androgen deprivation therapy (ADT) and AR pharmaco-antagonists (androgen insensitivity syndrome), two mainstream therapies in PCa [178,179]. Alterations in AR genes include point mutations and deletions.…”

Section: Metabolomics and Genomicsmentioning

confidence: 99%

The Integration of Metabolomics with Other Omics: Insights into Understanding Prostate Cancer

Resurreccion

Fong

2022

Metabolites

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Our understanding of prostate cancer (PCa) has shifted from solely caused by a few genetic aberrations to a combination of complex biochemical dysregulations with the prostate metabolome at its core. The role of metabolomics in analyzing the pathophysiology of PCa is indispensable. However, to fully elucidate real-time complex dysregulation in prostate cells, an integrated approach based on metabolomics and other omics is warranted. Individually, genomics, transcriptomics, and proteomics are robust, but they are not enough to achieve a holistic view of PCa tumorigenesis. This review is the first of its kind to focus solely on the integration of metabolomics with multi-omic platforms in PCa research, including a detailed emphasis on the metabolomic profile of PCa. The authors intend to provide researchers in the field with a comprehensive knowledge base in PCa metabolomics and offer perspectives on overcoming limitations of the tool to guide future point-of-care applications.

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“…Bipolar androgen therapy (BAT) refers to an innovative treatment approach for mCRPC that consists of the association of testosterone injections with regular ADT to reach transient supraphysiological testosterone levels [149]. Several clinical trials have reported the therapeutic effect of BAT on PSA decline and assessable imaging improvement [149,150]. BAT efficacy was recently evaluated in an open-label, phase-II, multicohort study of patients with mCRPC whose tumors had progressed after enzalutamide treatment.…”

Section: Potential Treatmentmentioning

confidence: 99%

Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment

2021

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Recent advances in prostate cancer (PC) research unveiled real androgen receptor (AR) functions in castration-resistant PC (CRPC). Moreover, AR still accelerates PC cell proliferation via the activation of several mechanisms (e.g., mutation, variants, and amplifications in CRPC). New-generation AR signaling-targeted agents, inhibiting extremely the activity of AR, were developed based on these incontrovertible mechanisms of AR-induced CRPC progression. However, long-term administration of AR signaling-targeted agents subsequently induces the major problem that AR (complete)-independent CRPC cells present neither AR nor prostate-specific antigen, including neuroendocrine differentiation as a subtype of AR-independent CRPC. Moreover, there are few treatments effective for AR-independent CRPC with solid evidence. This study focuses on the transformation mechanisms of AR-independent from AR-dependent CRPC cells and potential treatment strategy for AR-independent CRPC and discusses them based on a review of basic and clinical literature.

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The role of androgen therapy in prostate cancer: from testosterone replacement therapy to bipolar androgen therapy

Cited by 11 publications

References 84 publications

Sympathetic signaling facilitates progression of neuroendocrine prostate cancer

Sympathetic signaling facilitates progression of neuroendocrine prostate cancer

The Integration of Metabolomics with Other Omics: Insights into Understanding Prostate Cancer

Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment

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