The Current State of Hormonal Therapy for Prostate Cancer

Hellerstedt, Beth A.; Pienta, Kenneth J.

doi:10.3322/canjclin.52.3.154

Cited by 327 publications

(254 citation statements)

References 90 publications

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“…It is estimated that 10% of baseline testosterone levels are a result of peripheral conversion in the adrenal glands (46). It is also postulated that the adrenal production of androgens may be partially responsible for the progression to hormone-resistant prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effect of a novel antiandrogen, VN/124-1, and signal transduction inhibitors in prostate cancer progression to hormone independence in vitro

Schayowitz

Sabnis

Njar

et al. 2008

Molecular Cancer Therapeutics

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This study was carried out to determine the mechanisms associated with loss of androgen dependency and disease progression in prostate cancer. We investigated the role of the androgen receptor and its relationship to other signal transduction proteins. A hormone-refractory prostate cancer cell line [high-passage LNCaP (HP-LNCaP)] was established in vitro. Cells were treated with inhibitors of mammalian target of rapamycin and tyrosine kinase receptors. Expression of these proteins and the androgen receptor were measured by Western immunoblotting. Analysis of the model and various treatments was also assessed through proliferation assays, luciferase activation assays, binding assays, and ELISA. Our novel antiandrogen, VN/124-1, effectively inhibited proliferation of hormone-resistant prostate cancer cell lines (HP-LNCaP), which were no longer sensitive to bicalutamide and had increased expression of the androgen receptor. Treatment with everolimus or gefitinib resulted in an increase in protein expression and activation of the androgen receptor. Conversely, inhibition of the androgen receptor resulted in increased expression of IGFR1B, pHER2, pmTOR, and pAkt. The addition of bicalutamide to everolimus or gefitinib inhibited cell proliferation in HP-LNCaP cells. However, the addition of VN/124-1 has proven to be superior to bicalutamide, and the combination was synergistic (P < 0.05) compared with either agent alone. This study suggests that compensatory cross-talk between the androgen receptor and various signaling pathways may account for decreased sensitivity to androgen receptor antagonists and the progression to hormone-resistant prostate cancer. Furthermore, these findings suggest that inhibition of both pathways may provide effective control in hormone-resistant prostate cancer and restore sensitivity to androgen antagonists in hormone-refractory patients.

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Section: Discussionmentioning

confidence: 99%

Synergistic effect of a novel antiandrogen, VN/124-1, and signal transduction inhibitors in prostate cancer progression to hormone independence in vitro

Schayowitz

Sabnis

Njar

et al. 2008

Molecular Cancer Therapeutics

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“…80 The purpose of these pharmacological approaches is to lower androgen serum levels, which will induce a hormonal deregulation leading to leptin overexpression. 9 The unbalanced serum Obesity and prostate cancer R Ribeiro et al increase in leptin and decrease in androgens may facilitate androgen-independent cell growth, while downregulating androgen-dependent cells.…”

Section: Leptin and Pcamentioning

confidence: 99%

The link between obesity and prostate cancer: the leptin pathway and therapeutic perspectives

Ribeiro

Lopes

Medeiros

2005

Prostate Cancer Prostatic Dis

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Obesity-associated prostate cancer (PCa) remains controversial, although most studies rely on body mass index evaluation, which is an indirect measure of fatness. Studies using body fat measurement and disease stratification according to PCa stage found stronger associations between obesity and PCa. Leptin is a pleiotrophic hormone mainly synthesized by adipocytes that acts in peripheral organs such as the prostate. This article reviews obesity-associated leptin's pathophysiological role in PCa progression. PCa development results from some known risk factors. Currently, there is enough evidence suggesting that leptin is an additional factor involved in advanced PCa occurrence, and obesity association with high-grade disease. Life-long exposure to genetic and/or environmental susceptibility factors that predispose to obesity and higher leptin levels may increase the risk for advanced PCa.

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“…However, 80-90% of the patients develop androgen-independent tumors 12-33 months after androgen ablation therapy [18]. To study the progression of prostate cancer, we generated androgen-independent LNCaP sublines (104-R1, 104-R2, and CDXR) from an androgen-dependent LNCaP subline (104-S) after androgen deprivation [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

Chuu

Chen

Hiipakka

et al. 2007

Biochemical and Biophysical Research Communications

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T0901317 is a potent non-steroidal synthetic liver X receptor (LXR) agonist. T0901317 blocked androgenic stimulation of the proliferation of androgen-dependent LNCaP 104-S cells and androgenic suppression of the proliferation of androgen-independent LNCaP 104-R2 cells, inhibited the transcriptional activation of an androgen-dependent reporter gene by androgen, and suppressed gene and protein expression of prostate specific antigen (PSA), a target gene of androgen receptor (AR) without affecting gene and protein expression of AR. T0901317 also inhibited binding of a radiolabeled androgen to AR, but inhibition was much weaker compared to the effect of the antiandrogens, bicalutamide and hydroxyflutamide. The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells.

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The Current State of Hormonal Therapy for Prostate Cancer

Cited by 327 publications

References 90 publications

Synergistic effect of a novel antiandrogen, VN/124-1, and signal transduction inhibitors in prostate cancer progression to hormone independence in vitro

Synergistic effect of a novel antiandrogen, VN/124-1, and signal transduction inhibitors in prostate cancer progression to hormone independence in vitro

The link between obesity and prostate cancer: the leptin pathway and therapeutic perspectives

The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

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