Targeting the androgen receptor in metastatic castrate-resistant prostate cancer: A review

Anantharaman, Archana; Friedlander, Terence W.

doi:10.1016/j.urolonc.2015.11.003

Cited by 23 publications

(17 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…AR is a 920 residue-long ligand-activated transcription factor controlling expression of various eukaryotic genes and affecting proliferation and differentiation of cells in target tissues. AR plays a key role in the development and progression of prostate cancer and contributes to the development of resistance to androgen deprivation leading to the formation of the castration-resistant form of prostate cancer 102. There are several functional regions/domains in the AR.…”

Section: Discussionmentioning

confidence: 99%

Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

Landau

Schenck

et al. 2016

Asian J Androl

View full text Add to dashboard Cite

Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

Landau

Schenck

et al. 2016

Asian J Androl

View full text Add to dashboard Cite

show abstract

“…Molecular alterations render the AR less dependent on androgens for activation and include AR gene amplification and development of androgen hypersensitivity, AR mutations resulting in promiscuous ligand binding or androgen-independent activation, overactive AR variants, intratumoral androgen production, and mutations and deregulation of coactivators and corepressors 20,25,26. The molecular alterations of AR regulation and signaling in prostate cancer have been thoroughly reviewed in two recent excellent reviews 15,27. Typical cancer-related genomic alterations are also present in prostate cancer, including upregulation of cell survival and growth pathways, deregulation of cell cycle control, and inhibition of apoptosis 11,28.…”

Section: Molecular Alterations In Prostate Cancer and Current Therapiesmentioning

confidence: 99%

Oncolytic adenovirus-mediated therapy for prostate cancer

Sweeney

Halldén

2016

View full text Add to dashboard Cite

Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen–androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses.

show abstract

“…Androgens have an important role in the development and growth of the normal prostate gland, as well as in the proliferation of PCa cells (2,3). It has been reported that activation of the androgen receptor (AR) promotes the proliferation of PCa (3).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, androgen deprivation therapy (ADT) is considered the gold standard for the treatment of PCa recurrence and metastasis. However, despite a good initial response to ADT, the majority of patients progress to aggressive castration-resistant PCa (CRPC) within 2-3 years (2,4). Various mechanisms underlying resistance to ADT have been identified, including AR hypersensitivity, mutations, amplification and splicing variants, in addition to intratumoral steroidogenesis (3,4).…”

Section: Introductionmentioning

confidence: 99%

Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells

et al. 2018

View full text Add to dashboard Cite

Prostate cancer (PCa) is the second most common type of male malignancy worldwide. The transcription factor zinc finger E-box binding homeobox 1 (ZEB1) is associated with epithelial-mesenchymal transition and is also involved in regulation of androgen receptor (AR) expression, the main ligands of which are testosterone and dihydrotestosterone (DHT). These androgens are synthesized through the steroidogenic pathway within the prostate, and their synthesis is altered in PCa. The present study aimed to determine the ZEB1-induced alterations in androgen synthesis and AR expression in the DU145 PCa cell line. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunocytochemistry were used to determine the mRNA and protein expression levels, and cellular localization of steroidogenic pathway enzymes in the DU145 cell line in response to ZEB1 silencing. Furthermore, the concentrations of testosterone and DHT were detected in cell culture medium using ELISA. ZEB1-silenced cells exhibited an increase in testosterone and DHT production, an increase in AR expression and an alteration in the steroidogenic pathway. In particular, steroidogenic acute regulatory protein and 5α-reductase 2 expression levels were decreased, whereas cytochrome P450 family 17 subfamily A member 1, 5α-reductase 1, aldo-keto reductase family 1 member D1 and aldo-keto reductase family 1 member C2 expression levels were increased. In conclusion, the present study provided novel information regarding the regulation of intratumoral androgen production in PCa, which is relevant for the progression of the disease to a castration-resistant form.

show abstract

Targeting the androgen receptor in metastatic castrate-resistant prostate cancer: A review

Cited by 23 publications

References 90 publications

Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

Oncolytic adenovirus-mediated therapy for prostate cancer

Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells

Contact Info

Product

Resources

About