scholarly journals Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1133
Author(s):  
Fabrizio Fontana ◽  
Patrizia Limonta
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Castration Resistant Prostate Cancer ◽  
Therapeutic Implications ◽  
Androgen Synthesis ◽  
Castration Resistant ◽  
Camp Signaling Pathway ◽  
Expression Activity ◽  
Specific Receptors

Understanding the molecular mechanisms underlying prostate cancer (PCa) progression towards its most aggressive, castration-resistant (CRPC) stage is urgently needed to improve the therapeutic options for this almost incurable pathology. Interestingly, CRPC is known to be characterized by a peculiar hormonal landscape. It is now well established that the androgen/androgen receptor (AR) axis is still active in CRPC cells. The persistent activity of this axis in PCa progression has been shown to be related to different mechanisms, such as intratumoral androgen synthesis, AR amplification and mutations, AR mRNA alternative splicing, increased expression/activity of AR-related transcription factors and coregulators. The hypothalamic gonadotropin-releasing hormone (GnRH), by binding to its specific receptors (GnRH-Rs) at the pituitary level, plays a pivotal role in the regulation of the reproductive functions. GnRH and GnRH-R are also expressed in different types of tumors, including PCa. Specifically, it has been demonstrated that, in CRPC cells, the activation of GnRH-Rs is associated with a significant antiproliferative/proapoptotic, antimetastatic and antiangiogenic activity. This antitumor activity is mainly mediated by the GnRH-R-associated Gαi/cAMP signaling pathway. In this review, we dissect the molecular mechanisms underlying the role of the androgen/AR and GnRH/GnRH-R axes in CRPC progression and the possible therapeutic implications.

scholarly journals Role of Signaling Transduction Pathways in Development of Castration-Resistant Prostate Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takahiro Inoue ◽  
Osamu Ogawa
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Castration Resistant Prostate Cancer ◽  
Novel Treatments ◽  
Resistant Disease ◽  
Castration Resistant ◽  
Almost All

Almost all patients who succumb to prostate cancer die of metastatic castration-resistant disease. Although docetaxel is the standard treatment for this disease and is associated with modest prolongation of survival, there is an urgent need for novel treatments for castration-resistant prostate cancer (CRPC). Great advances in our understanding of the biological and molecular mechanisms of prostate cancer progression have resulted in many clinical trials of numerous targeted therapies. In this paper, we review mechanisms of CRPC development, with particular focus on recent advances in the understanding of specific intracellular signaling pathways participating in the proliferation of CRPC cells.

AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

2018 ◽  
Vol 18 (9) ◽  
pp. 869-876
Author(s):  
Samanta Salvi ◽  
Vincenza Conteduca ◽  
Cristian Lolli ◽  
Sara Testoni ◽  
Valentina Casadio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Clinical Trial Design ◽  
Complete Information ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Cancer ◽  
Hormone Sensitive ◽  
Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

The role of abiraterone in the management of metastatic castration-resistant prostate cancer

2012 ◽  
Vol 12 (4) ◽  
pp. 429-437 ◽  
Author(s):  
Alex Rawlinson ◽  
Aza Mohammed ◽  
John Beatty ◽  
Richard Bell ◽  
Marek Miller
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
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