scholarly journals Role of the Androgen-Androgen Receptor Axis in the Treatment Resistance of Advanced Prostate Cancer: From Androgen-Dependent to Castration Resistant and Further

2016 ◽  
Vol 38 (2) ◽  
pp. 129-138 ◽  
Author(s):  
Naohiro FUJIMOTO
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Advanced Prostate Cancer ◽  
Treatment Resistance ◽  
Castration Resistant

scholarly journals Enzalutamide therapy for advanced prostate cancer: efficacy, resistance and beyond

2019 ◽  
Vol 26 (1) ◽  
pp. R31-R52 ◽  
Author(s):  
Simon Linder ◽  
Henk G van der Poel ◽  
Andries M Bergman ◽  
Wilbert Zwart ◽  
Stefan Prekovic
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Advanced Prostate Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Castration Resistant ◽  
Novel Drugs

The androgen receptor drives the growth of metastatic castration-resistant prostate cancer. This has led to the development of multiple novel drugs targeting this hormone-regulated transcription factor, such as enzalutamide – a potent androgen receptor antagonist. Despite the plethora of possible treatment options, the absolute survival benefit of each treatment separately is limited to a few months. Therefore, current research efforts are directed to determine the optimal sequence of therapies, discover novel drugs effective in metastatic castration-resistant prostate cancer and define patient subpopulations that ultimately benefit from these treatments. Molecular studies provide evidence on which pathways mediate treatment resistance and may lead to improved treatment for metastatic castration-resistant prostate cancer. This review provides, firstly a concise overview of the clinical development, use and effectiveness of enzalutamide in the treatment of advanced prostate cancer, secondly it describes translational research addressing enzalutamide response vs resistance and lastly highlights novel potential treatment strategies in the enzalutamide-resistant setting.

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.

scholarly journals Androgen receptor antagonists for prostate cancer therapy

2014 ◽  
Vol 21 (4) ◽  
pp. T105-T118 ◽  
Author(s):  
Christine Helsen ◽  
Thomas Van den Broeck ◽  
Arnout Voet ◽  
Stefan Prekovic ◽  
Hendrik Van Poppel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Androgen Receptor ◽  
Metastatic Prostate Cancer ◽  
Castration Resistant ◽  
Androgen Action ◽  
Conflicting Evidence ◽  
Prostate Cancer Therapy ◽  
Androgen Receptor Antagonists

Androgen deprivation is the mainstay therapy for metastatic prostate cancer (PCa). Another way of suppressing androgen receptor (AR) signaling is via AR antagonists or antiandrogens. Despite being frequently prescribed in clinical practice, there is conflicting evidence concerning the role of AR antagonists in the management of PCa. In the castration-resistant settings of PCa, docetaxel has been the only treatment option for decades. With recent evidence that castration-resistant PCa is far from AR-independent, there has been an increasing interest in developing new AR antagonists. This review gives a concise overview of the clinically available antiandrogens and the experimental AR antagonists that tackle androgen action with a different approach.

scholarly journals Second-generation androgen receptor inhibitors in therapy of non-metastatic castration resistant prostate cancer: role of safety profile and effect on quality of life

2021 ◽  
Vol 67 (2) ◽  
pp. 217-226
Author(s):  
Elena Ushkalova ◽  
Sergey Zyryanov ◽  
Irina Gopienko
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Safety Profile ◽  
Second Generation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Clinically Significant

The article discusses the role of second-generation androgen receptor inhibitors (ARi) in therapy of non-metastatic castration resistant prostate cancer (nmCRPC). The phase 3 trials PROSPER (enzalutamide), SPARTAN (apalutamide) and ARAMIS (darolutamide) showed that these medicines if used in combination with androgen deprivation therapy (ADT) make possible to significantly improve, as compared with placebo, metastasis-free survival and overall survival of patients with nmCRPC. An important role in choosing a certain medicine of the group is played by its safety profile, including its drug-drug interaction potential and effect on patient’s quality of life. In this respect, darolutamide has a number of advantages over apalutamide or enzlutamide. The frequency of CNS (cognitive, psychiatric, convulsive) and other adverse drug reactions that significantly worsen the patients’ quality of life (falls, fractures, hypertension, etc.) in therapy with darolutamide does not differ from that with placebo. Moreover, this medicine retains its antagonistic effects to all clinically significant androgen receptor mutations that develop resistance to enzalutamide and apalutamide.

scholarly journals Extracellular Vesicles in Advanced Prostate Cancer: Tools to Predict and Thwart Therapeutic Resistance

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3791
Author(s):  
Carolina Saldana ◽  
Amene Majidipur ◽  
Emma Beaumont ◽  
Eric Huet ◽  
Alexandre de la Taille ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Extracellular Vesicles ◽  
Advanced Prostate Cancer ◽  
Initial Response ◽  
Therapeutic Resistance ◽  
Cancer Death ◽  
Cellular Mechanisms

Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death among men worldwide. At first, advanced PCa is treated by androgen deprivation therapy with a good initial response. Nevertheless, recurrences occur, leading to Castrate-Resistance Prostate Cancer (CRPC). During the last decade, new therapies based on inhibition of the androgen receptor pathway or taxane chemotherapies have been used to treat CRPC patients leading to an increase in overall survival, but the occurrence of resistances limits their benefits. Numerous studies have demonstrated the implication of extracellular vesicles (EVs) in different cancer cellular mechanisms. Thus, the possibility to isolate and explore EVs produced by tumor cells in plasma/sera represents an important opportunity for the deciphering of those mechanisms and the discovery of biomarkers. Herein, we summarized the role of EVs in therapeutic resistance of advanced prostate cancer and their use to find biomarkers able to predict these resistances.

scholarly journals Long non-coding RNAs in castration-resistant and neuroendocrine prostate cancer: Potential role and therapeutic impact

2020 ◽  
pp. 18-22
Author(s):  
Kumari S. Prajapati ◽  
Atul K. Singh ◽  
Mohd Shuaib ◽  
Prem P. Kushwaha ◽  
Shashank Kumar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Potential Role ◽  
Mechanisms Of Action ◽  
Biological Processes ◽  
Cognate Receptor ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Non Coding Rnas

Prostate cancer is the most commonly diagnosed malignancy and leading cause of cancer-related deaths in men worldwide. The disease is heterogeneous in nature exhibiting various clinical subtypes and genetic/transcriptomic features. Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that does not encode any protein and play important role in several biological processes as well as pathologic states. Deregulation of lncRNAs has been associated with human diseases. In prostate cancer, numerous key lncRNAs have been identified as novel players that contribute to the pathophysiology of the disease primarily regulated by androgen and its cognate receptor. The present review attempts to summarize the potential role of lncRNA and their mechanisms of action in prostate cancer with particular focus on lncRNAs regulated by androgen receptor expressed in castration-resistant and neuroendocrine differentiated subtypes. We also emphasize the potential of these lncRNAs for their development as therapeutic targets in prostate cancer.

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