Article

Perlmutter MA, Lepor H. Androgen deprivation therapy in the treatment of advanced prostate cancer. Rev Urol. 9:(Suppl 1):S3-S8

Department of Urology, New York University School of Medicine New York, NY.
Reviews in urology 02/2007; 9 Suppl 1(supplement 1):S3-8.
Source: PubMed

ABSTRACT

This article reviews the issues and controversies relevant to the treatment of advanced prostate cancer with androgen deprivation therapy. Initially, diethylstilbestrol was used for achieving androgen deprivation, but was replaced by luteinizing hormone-releasing hormone (LHRH). Adverse events associated with LHRH agonists include the flare phenomenon, hot flashes, loss of libido, erectile dysfunction, depression, muscle wasting, anemia, and osteoporosis. Intermittent therapy has been advocated to reduce morbidity of treatment. The addition of an antiandrogen provides maximum androgen blockade. There remains controversy regarding the timing of the addition of an antiandrogen. Secondary hormonal therapies include antiandrogens, adrenal androgen inhibitors, and estrogens.

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    • "In xenograft experiments, polyamide 1 has been shown to be active towards LNCaP xenografts at doses of 1 mg/kg[19]. LNCaP, however, expresses a mutated androgen receptor, and as a result, may not be representative of the majority of human disease[22]. It would therefore be useful to evaluate the efficacy of 1 against other forms of prostate cancer. "
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    ABSTRACT: Pyrrole-imidazole (Py-Im) polyamides are high affinity DNA-binding small molecules that can inhibit protein-DNA interactions. In VCaP cells, a human prostate cancer cell line overexpressing both AR and the TMPRSS2-ERG gene fusion, an androgen response element (ARE)-targeted Py-Im polyamide significantly downregulates AR driven gene expression. Polyamide exposure to VCaP cells reduced proliferation without causing DNA damage. Py-Im polyamide treatment also reduced tumor growth in a VCaP mouse xenograft model. In addition to the effects on AR regulated transcription, RNA-seq analysis revealed inhibition of topoisomerase-DNA binding as a potential mechanism that contributes to the antitumor effects of polyamides in cell culture and in xenografts. These studies support the therapeutic potential of Py-Im polyamides to target multiple aspects of transcriptional regulation in prostate cancers without genotoxic stress.
    Full-text · Article · Nov 2015 · PLoS ONE
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    • "Androgen deprivation therapy (ADT) is undoubtedly the mainstay of treatment for symptomatic metastatic prostate cancer. Although ADT indications are limited to the palliation of symptomatic metastases, ADT is widely used in men with biochemical (PSA) relapse after radical prostatectomy, locally advanced disease, lymph node metastases, and also asymptomatic metastatic disease [2] [3]. ADT is also commonly used in combination with external beam radiotherapy (EBRT) for intermediate to high-risk prostate cancer cases in order to improve responses to radiotherapy [4]. "

    Full-text · Dataset · Jul 2013
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    • "Androgen deprivation therapy (ADT) is undoubtedly the mainstay of treatment for symptomatic metastatic prostate cancer. Although ADT indications are limited to the palliation of symptomatic metastases, ADT is widely used in men with biochemical (PSA) relapse after radical prostatectomy, locally advanced disease, lymph node metastases, and also asymptomatic metastatic disease [2] [3]. ADT is also commonly used in combination with external beam radiotherapy (EBRT) for intermediate to high-risk prostate cancer cases in order to improve responses to radiotherapy [4]. "
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    ABSTRACT: The prostate is an androgen-dependent organ. The increase, growth, homeostasis, and function of the prostate largely depend upon the intraprostatic and serum concentrations of androgens. Therefore, androgens are essential for the physiologic growth of prostatic epithelium. Prostate cancer, the second leading cause of death for men, is also androgen dependent, and androgen suppression is the mainstay of treatment for advanced and metastatic disease. In the state of metastatic disease, androgen suppression is a palliative treatment leading to a median progression-free survival of 18-20 months and an overall survival of 24-36 months. Theoretically, the majority of patients will develop hormone-refractory disease provided that they will not die from other causes. Although androgen suppression therapy may be associated with significant and sometimes durable responses, it is not considered a cure, and its potential efficacy is further limited by an array of significant and bothersome adverse effects caused by the suppression of androgens. These effects have potentially significant consequences on a variety of parameters of everyday living and may further decrease health-related quality of life. This review focuses on the aetiology of these adverse effects and provides information on their prevention and management.
    Full-text · Article · Jul 2013
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