Hormonal and Chemotherapeutic Systemic Therapy for Metastatic Prostate Cancer

1996 ◽  
Vol 3 (6) ◽  
pp. 493-500 ◽  
Author(s):  
Ravat Panvichian ◽  
Kenneth J. Pienta
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Patient Survival ◽  
Tumor Biology ◽  
The United States ◽  
Hormone Refractory Prostate Cancer ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Hormone Refractory ◽  
Androgen Ablation Therapy

Background Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. It is estimated that over 300,000 men will have been diagnosed with prostate cancer in 1996, and more than 40,000 will have died of this disease. Methods The authors combined their experience with a review of the literature on management of this disease to examine the effectiveness of treatments for both localized and metastatic prostate cancer. Results Surgery and radiation therapy are potentially curative modalities for cancer still limited to the gland. Androgen ablation therapy results in stabilization or regression of metastatic disease in most instances but is not curative. Some new approaches are described for patients with hormone-refractory prostate cancer. Conclusions Newer tumor-biology-based combinations are promising in the treatment of hormone-refractory prostate cancer, but their effect on patient survival needs to be evaluated in larger clinical trials.

Androgen-regulated metabolome in prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 25-25
Author(s):  
N. Putluri ◽  
Y. Zhang ◽  
V. Putluri ◽  
S. Vareed ◽  
V. T. Vasu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Prostate Epithelial Cells ◽  
Number Of Patients ◽  
Hormone Refractory ◽  
Androgen Ablation Therapy

25 Background: Prostate cancer (PC) is the second most prevalent cancer among American men which is primarily treated by androgen ablation therapy. Although a number of patients respond to this regimen, a significant subset fail and the tumor invariably progresses into a hormone refractory metastatic state, which is lethal. Earlier we had reported the first unbiased metabolomic signature for localized and metastatic prostate cancer tissues. Advancing further, we attempt to delineate the subset of metabolome in prostate cancer which is regulated by androgen-action. Methods: Androgen responsive (R22V1, LnCap and VCAP) and independent (PC3, DU145) PC cells and benign prostate epithelial cells (RWPE) were profiled for their metabolomic alterations using mass spectrometry. Extracted metabolome from these cells were profiles using a combination quadrupole-time-of-flight (Q-TOF) and triple quadrupole (QQQ) mass spectrometers coupled to reverse phase and aqueous normal phase chromatography. The metabolomic profiles were analyzed to delineate class-specific signatures which were interrogated for altered bioprocesses using Oncomine Concept Map (OCM, www.oncomine.org ). The androgen receptor (AR) regulated metabolome was verified using treatment of PC cells with synthetic androgen, R1881. Results: A total of 3,092 metabolites (113 named) were detected across the 4 cells lines, of which 869 compounds were significantly (ANOVA P<0.01) different between androgen responsive and non-responsive cells. The differential compendia included 28 named metabolites, including sarcosine which was earlier shown to be elevated during PC development and progression. Bioprocess mapping of AR-regulated metabolome revealed enrichment of amino acid metabolism and methylation potential, both of which were earlier defined to be the hallmarks of PC development and progression. Conclusions: The study defines AR-regulated metabolic signature which portrays enrichment of amino acid metabolism and methylation potential that are hallmarks of PC development and progression. No significant financial relationships to disclose.

scholarly journals Hormonal therapy in metastatic prostate cancer: current perspectives and controversies

2013 ◽  
pp. e6
Author(s):  
Manish Garg ◽  
Vishwajeet Singh ◽  
Manoj Kumar ◽  
Satya Narayan Sankhwar
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Metastatic Prostate Cancer ◽  
Treatment Guidelines ◽  
Negative Impact ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Tremendous Progress ◽  
Androgen Ablation Therapy

Ever since the introduction of androgen deprivation therapy (ADT) in prostate cancer, various controversial aspects of hormonal therapy have come to light. There has been tremendous progress in this area, marked by several important developments in the availability of various new androgen-suppressing agents and refinements to the existing therapies. Parallel to these developments, various more debatable aspects have arisen in the use of these therapies with regards to their negative impact on quality of life parameters. Various modifications in these hormonal agents, their doses, and protocols have been tried in different scenarios in order to improve ADT tolerability. As a result, these controversies continue to evolve even with optimal use of the androgen ablation therapy. This review assesses the present status of hormonal therapy in metastatic prostate cancer and specifically deals with those aspects of androgen ablation therapy that are still a subject of debate. In spite of the fact that various trials have been conducted, some of which are still ongoing, the multitude of questions related to the best possible use of these hormonal agents have still not been answered. Treatment guidelines concerning these issues are continuing to evolve as progress continues to be made in this field.

scholarly journals COST-UTILITY ANALYSIS OF ANDROGEN ABLATION THERAPY IN METASTATIC PROSTATE CANCER

2003 ◽  
Vol 94 (4) ◽  
pp. 503-512
Author(s):  
Keita Fujikawa ◽  
Yasuo Awakura ◽  
Tatsushiro Okabe ◽  
Rei Watanabe ◽  
Shuzo Nishimura
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Cost Utility ◽  
Cost Utility Analysis ◽  
Utility Analysis ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Androgen Ablation Therapy

scholarly journals Hormonal therapy in metastatic prostate cancer: current perspectives and controversies

2013 ◽  
Vol 7 (1) ◽  
pp. 6
Author(s):  
Manish Garg ◽  
Vishwajeet Singh ◽  
Manoj Kumar ◽  
Satya Narayan Sankhwar
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Metastatic Prostate Cancer ◽  
Treatment Guidelines ◽  
Negative Impact ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Tremendous Progress ◽  
Androgen Ablation Therapy

Ever since the introduction of androgen deprivation therapy (ADT) in prostate cancer, various controversial aspects of hormonal therapy have come to light. There has been tremendous progress in this area, marked by several important developments in the availability of various new androgen-suppressing agents and refinements to the existing therapies. Parallel to these developments, various more debatable aspects have arisen in the use of these therapies with regards to their negative impact on quality of life parameters. Various modifications in these hormonal agents, their doses, and protocols have been tried in different scenarios in order to improve ADT tolerability. As a result, these controversies continue to evolve even with optimal use of the androgen ablation therapy. This review assesses the present status of hormonal therapy in metastatic prostate cancer and specifically deals with those aspects of androgen ablation therapy that are still a subject of debate. In spite of the fact that various trials have been conducted, some of which are still ongoing, the multitude of questions related to the best possible use of these hormonal agents have still not been answered. Treatment guidelines concerning these issues are continuing to evolve as progress continues to be made in this field.

scholarly journals Crosstalk Between Nuclear MET and SOX9/β-Catenin Correlates with Castration-Resistant Prostate Cancer

2014 ◽  
Vol 28 (10) ◽  
pp. 1629-1639 ◽  
Author(s):  
Yingqiu Xie ◽  
Wenfu Lu ◽  
Shenji Liu ◽  
Qing Yang ◽  
Brett S. Carver ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combined Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Castration Resistant ◽  
Activate Cell ◽  
Androgen Ablation Therapy

Castration-resistant prostate cancer (PCa) (CRPC) is relapse after various forms of androgen ablation therapy and causes a major mortality in PCa patients, yet the mechanism remains poorly understood. Here, we report the nuclear form of mesenchymal epithelial transition factor (nMET) is essential for CRPC. Specifically, nMET is remarkably increased in human CRPC samples compared with naïve samples. Androgen deprivation induces endogenous nMET and promotes cell proliferation and stem-like cell self-renewal in androgen-nonresponsive PCa cells. Mechanistically, nMET activates SRY (sex determining region Y)-box9, β-catenin, and Nanog homeobox and promotes sphere formation in the absence of androgen stimulus. Combined treatment of MET and β-catenin enhances the inhibition of PCa cell growth. Importantly, MET accumulation is detected in nucleus of recurrent prostate tumors of castrated Pten/Trp53 null mice, whereas MET elevation is predominantly found in membrane of naïve tumors. Our findings reveal for the first time an essential role of nMET association with SOX9/β-catenin in CRPC in vitro and in vivo, highlighting that nuclear RTK activate cell reprogramming to drive recurrence, and targeting nMET would be a new avenue to treat recurrent cancers.

scholarly journals α-Actinin-4 Promotes the Progression of Prostate Cancer Through the Akt/GSK-3β/β-Catenin Signaling Pathway

2020 ◽  
Vol 8 ◽  
Author(s):  
Sungyeon Park ◽  
Minsoo Kang ◽  
Suhyun Kim ◽  
Hyoung-Tae An ◽  
Jan Gettemans ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Actin Binding ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Proliferation And Metastasis ◽  
Gsk 3Β ◽  
Androgen Ablation Therapy

The first-line treatment for prostate cancer (PCa) is androgen ablation therapy. However, prostate tumors generally recur and progress to androgen-independent PCa (AIPC) within 2–3 years. α-Actinin-4 (ACTN4) is an actin-binding protein that belongs to the spectrin gene superfamily and acts as an oncogene in various cancer types. Although ACTN4 is involved in tumorigenesis and the epithelial–mesenchymal transition of cervical cancer, the role of ACTN4 in PCa remains unknown. We found that the ACTN4 expression level increased during the transition from androgen-dependent PCa to AIPC. ACTN4 overexpression resulted in enhanced proliferation and motility of PCa cells. Increased β-catenin due to ACTN4 promoted the transcription of genes involved in proliferation and metastasis such as CCND1 and ZEB1. ACTN4-overexpressing androgen-sensitive PCa cells were able to grow in charcoal-stripped media. In contrast, ACTN4 knockdown using si-ACTN4 and ACTN4 nanobody suppressed the proliferation, migration, and invasion of AIPC cells. Results of the xenograft experiment revealed that the mice injected with LNCaPACTN4 cells exhibited an increase in tumor mass compared with those injected with LNCaPMock cells. These results indicate that ACTN4 is involved in AIPC transition and promotes the progression of PCa.

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