MedWorm: Hormone Resistant Prostate Cancer

Scientists Find Key to Hormone-Resistant Prostate Tumors

MedicineNet Cancer General — Thu, 11 Mar 2010 07:00:00 +0100

Title: Scientists Find Key to Hormone-Resistant Prostate TumorsCategory: Health NewsCreated: 3/10/2010 2:10:00 PMLast Editorial Review: 3/11/2010 (Source: MedicineNet Cancer General)

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Scientists Find Key to Hormone-Resistant Prostate Tumors

MedicineNet Menopause General — Thu, 11 Mar 2010 07:00:00 +0100

Title: Scientists Find Key to Hormone-Resistant Prostate TumorsCategory: Health NewsCreated: 3/10/2010 2:10:00 PMLast Editorial Review: 3/11/2010 (Source: MedicineNet Menopause General)

Scientists Find Key to Hormone-Resistant Prostate Tumors

MedicineNet Mens Health General — Thu, 11 Mar 2010 07:00:00 +0100

Title: Scientists Find Key to Hormone-Resistant Prostate TumorsCategory: Health NewsCreated: 3/10/2010 2:10:00 PMLast Editorial Review: 3/11/2010 (Source: MedicineNet Mens Health General)

Scientists Find Key to Hormone-Resistant Prostate Tumors

MedlinePlus Health News — Wed, 10 Mar 2010 19:00:00 +0100

Discovery in mouse study may someday extend men's lives Source: HealthDay Related MedlinePlus Pages: Hormones, Prostate Cancer (Source: MedlinePlus Health News)

Harbor BioSciences Reports New Phase I/IIa Data at ASCO Symposium and Announces Plans to Advance Prostate Cancer Treatment Apoptone(R) to Phase IIb

Medical News (via PRIMEZONE) — Mon, 08 Mar 2010 13:00:00 +0100

SAN DIEGO, March 8, 2010 (GLOBE NEWSWIRE) -- Harbor BioSciences Inc. (Nasdaq:HRBR) said today it had reported encouraging data from its ongoing Phase I/IIa clinical trial with Apoptone(r) (HE3235) for castration resistant prostate cancer (CRPC) -- also referred to as hormone resistant prostate cancer -- at the ASCO Genitourinary Cancers Symposium in San Francisco on March 6, 2010. Preliminary results from this study, conducted with participating member sites of the Prostate Cancer Clinical Trial Consortium (PCCTC), were first reported on November 16, 2009. Apoptone is a novel steroid analog of a dihydrotestosterone metabolite that has been found to induce cell death (apoptosis) in prostate tumors. (Source: Medical News (via PRIMEZONE))

PSA Decrease with Fulvestrant Acetate in a Hormone-Resistant Metastatic Prostate Cancer Patient.

Onkologie — Fri, 19 Feb 2010 21:40:04 +0100

Conclusion: Fulvestrant was able to reduce the PSA level in this AIPC patient without any toxicity. PMID: 20164664 [PubMed - as supplied by publisher] (Source: Onkologie)

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Inhibition of Epidermal Growth Factor Receptor Signaling by Saussurea involucrata, a Rare Traditional Chinese Medicinal Herb, in Human Hormone-Resistant Prostate Cancer PC-3 Cells

Journal of Agricultural and Food Chemistry — Thu, 18 Feb 2010 13:13:12 +0100

Journal of Agricultural and Food Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Agricultural and Food Chemistry)

More blood vessels in hormone-resistant prostate tumors

ScienceDaily Headlines — Wed, 16 Dec 2009 13:00:00 +0100

Patients with advanced prostate cancer are often treated with hormones, but when the tumors start growing again they have more and different blood vessels, reveals research from Sweden. This discovery paves the way for new treatments for hormone-resistant prostate cancer. (Source: ScienceDaily Headlines)

More Blood Vessels In Hormone-resistant Prostate Tumours

Health News from Medical News Today — Wed, 16 Dec 2009 09:00:00 +0100

Patients with advanced prostate cancer are often treated with hormones, but when the tumours start growing again they have more and different blood vessels, reveals a thesis from the Sahlgrenska Academy, at the University of Gothenburg, Sweden. This discovery paves the way for new treatments for hormone-resistant prostate cancer. Late in the course of the disease, when the prostate cancer has spread, most patients are given hormone therapy. This reduces the production of the male sex hormone and the tumour shrinks... (Source: Health News from Medical News Today)

More Blood Vessels In Hormone-resistant Prostate Tumours

Endocrinology News From Medical News Today — Wed, 16 Dec 2009 09:00:00 +0100

More Blood Vessels In Hormone-resistant Prostate Tumours

Endocrinology News From Medical News Today — Wed, 16 Dec 2009 09:00:00 +0100

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More blood vessels in hormone-resistant prostate tumors

EurekAlert! - Social and Behavioral Science — Tue, 15 Dec 2009 05:00:00 +0100

(University of Gothenburg) Patients with advanced prostate cancer are often treated with hormones, but when the tumours start growing again they have more and different blood vessels, reveals a thesis from the Sahlgrenska Academy, at the University of Gothenburg, Sweden. This discovery paves the way for new treatments for hormone-resistant prostate cancer. (Source: EurekAlert! - Social and Behavioral Science)

Hollis-Eden Presents New Interim Data From Prostate Cancer Phase I/II Clinical Studies Of Apoptone (HE3235) At AACR Molecular Targets Conference

Health News from Medical News Today — Tue, 17 Nov 2009 09:00:00 +0100

Hollis-Eden Pharmaceuticals, Inc. (Nasdaq: HEPH), reported preliminary results of its ongoing Phase I/II clinical trial with Apoptone® (HE3235) for hormone-resistant prostate cancer (also called castrate-resistant prostate cancer or CRPC). (Source: Health News from Medical News Today)

Hollis-Eden Presents New Interim Data From Prostate Cancer Phase I/II Clinical Studies Of Apoptone (HE3235) At AACR Molecular Targets Conference

Pharma Industry News From Medical News Today — Tue, 17 Nov 2009 09:00:00 +0100

Hollis-Eden Presents New Interim Data From Prostate Cancer Phase I/II Clinical Studies Of Apoptone (HE3235) At AACR Molecular Targets And Cancer Therapeutics Conference

Pharmaceutical Online News — Mon, 16 Nov 2009 10:11:00 +0100

Hollis-Eden Pharmaceuticals, Inc. (Nasdaq: HEPH ), today reported preliminary results of its ongoing Phase I/II clinical trial with Apoptone® (HE3235) for hormone-resistant prostate cancer (also called castrate-resistant prostate cancer or CRPC). (Source: Pharmaceutical Online News)

Docetaxel-ST1481 sequence exerts a potent cytotoxic activity on hormone-resistant prostate cancer cells by reducing drug resistance-related gene expression

The Prostate — Mon, 28 Sep 2009 23:00:00 +0100

The efficacy of current therapy for hormone-refractory prostate cancer is still unsatisfactory and new agents and therapeutic modalities are needed. The aims of the present work were to examine the in vitro activity and mechanisms of action of different antitumor drug combinations in hormone-resistant prostate cancer (HRPC) cell lines.The activity of docetaxel (Doc), cisplatin (Cis), oxaliplatin (Oxa), SN-38 and ST1481, singly or in combination, was assessed in different HRPC cell lines (PC3, parental DU145 and taxane-resistant DU145-R) by SRB test. Apoptosis was evaluated by TUNEL and ANN-V assays. Extrusion pump activity was studied by Hoechst 33342 assay, while gene expression related to drug efflux mechanisms and DNA damage repair was analyzed by RT-PCR.Doc induced a high cytocidal eff...

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Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r

Magnetic Resonance in Medicine — Wed, 23 Sep 2009 23:00:00 +0100

In this study, total choline distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before and at 4 h and 48 h after a single-bolus 17-allylamino, 17-demethoxygeldanamycin treatment at 100 mg/kg, using proton MR spectroscopy. Our results show that tumor total choline levels declined 4 h after the treatment for CWR22 (P = 0.001) and 48 h post treatment for CWR22r (P = 0.003). Metabolic changes, in particular of total choline intensity detected by proton magnetic resonance spectroscopic imaging (MRSI), are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P = 0.01 at 14 days post treatment), and a constant prostate specific antigen level versus increasing prostate specific antig...

Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r.

Magnetic Resonance in Medicine — Wed, 23 Sep 2009 23:00:00 +0100

A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression

BMC Genomics - Latest articles — Tue, 28 Jul 2009 23:00:00 +0100

Conclusions: The SIG method reliably identifies cancer progression correlated gene pairs, and performs well both in gene pair ontology analysis and in pathway enrichment analysis. So, this method may provide an effective means of understanding the molecular mechanism of carcinogenesis by appropriately tracking down the process of cancer progression. (Source: BMC Genomics - Latest articles)

Annexin-A7 protects normal prostate cells and induces distinct patterns of RB-associated cytotoxicity in androgen-sensitive and -resistant prostate cancer cells

International Journal of Cancer — Thu, 16 Jul 2009 23:00:00 +0100

The tumor suppressor role of annexin-A7 (ANXA7) was previously demonstrated by cancer susceptibility in Anxa7(+/-)-mice and by ANXA7 loss in human cancers, especially in hormone-resistant prostate tumors. To gain mechanistic insights into ANXA7 tumor suppression, we undertook an in vitro study in which we compared wild-type (WT)-ANXA7 and dominant-negative (DN)-ANXA7 effects to a conventional tumor suppressor p53 in prostate cancer cells with different androgen sensitivity. Unlike p53 (which caused cell growth arrest and apoptosis to a noticeable extent in benign PrEC), WT-ANXA7 demonstrated profound cytotoxicityin androgen-sensitive LNCaP as well as in the androgen-resistant DU145 and PC3 prostate cancer cells, but not in PrEC. In androgen-sensitive LNCaP, WT-ANXA7 decreased low-molecular...

Antitumor Activity with CYP17 Blockade Indicates That Castration-Resistant Prostate Cancer Frequently Remains Hormone Driven

Cancer Research — Mon, 15 Jun 2009 04:00:00 +0100

Abiraterone acetate is a potent, selective, and orally bioavailable small molecule inhibitor of CYP17, an enzyme that catalyzes two key serial reactions (17 alpha hydroxylase and 17,20 lyase) in androgen and estrogen biosynthesis. Clinical trials have confirmed that specific inhibition of CYP17 is safe and results in clinically important antitumor activity in up to 70% of castrate patients with advanced prostate cancer resistant to currently available endocrine therapies. These clinical data indicate that castration-resistant prostate cancer frequently remains hormone dependent and has confirmed that this disease should no longer be described as "hormone resistant or refractory". Biomarker studies, including the analysis of ETS gene fusion status, on patients treated with abiraterone aceta...

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Sphingosine kinase 1 inhibition sensitizes hormone-resistant prostate cancer to docetaxel

International Journal of Cancer — Wed, 10 Jun 2009 23:00:00 +0100

In this study we have addressed the mechanism of docetaxel-induced apoptosis of PC-3 cells and identified SphK1-dependent and -independent components. We have shown that SphK1 inhibition by docetaxel is a two-step process involving an initial loss of enzyme activity followed by a decrease in SphK1 gene expression. Using hormoneresistant PC-3 and DU145 PCa cells we have demonstrated that both pharmacological and siRNA-mediated SphK1 inhibition leads to a four-fold decrease in the docetaxel IC50 dose. This work points out to potential ways of increasing the effectiveness of chemotherapy for PCa by SphK1 inhibition. © 2009 UICC (Source: International Journal of Cancer)

In vitro metabolism of the specific endothelin-A receptor antagonist ZD4054 and clinical drug interactions between ZD4054 and rifampicin or itraconazole in healthy male volunteers.

Xenobiotica — Sun, 31 May 2009 23:00:00 +0100

Authors: Swaisland HC, Oliver SD, Morris T, Jones HK, Bakhtyari A, Mackey A, McCormick AD, Slamon D, Hargreaves JA, Millar A, Taboada MT ZD4054 is an oral specific endothelin-A receptor antagonist in development for the treatment of hormone-resistant prostate cancer. Both renal and metabolic processes contribute to its overall clearance. Two preclinical in vitro studies investigated the metabolism of ZD4054 using human liver microsomes, individual cytochrome P450 (CYP) isozymes, and flavin-containing monooxygenase isoforms. Two Phase I open-label crossover volunteer studies subsequently investigated in vivo drug interactions between ZD4054 and the CYP450 inducer rifampicin or CYP3A4 inhibitor itraconazole. The most abundant metabolite produced in in vitro incubations accounted for 12.8...

PSA Decrease with Fulvestrant Acetate in a Hormone-Resistant Metastatic Prostate Cancer Patient: A Case Report

Karger Publishers — Fri, 24 Apr 2009 15:27:06 +0100

Case Rep Oncol 2009;2:72-76 (DOI:10.1159/000214838) (Source: Karger Publishers)

AR signature may improve hormone-resistant prostate cancer therapy

MedWire News - Oncology — Wed, 22 Apr 2009 16:23:49 +0100

A novel transcription-based activity signature is able to detect androgen receptor activity within individual prostate cancer specimens, say US scientists whose findings may help to improve care for patients with castration-resistant tumors. (Source: MedWire News - Oncology)

AR signature may improve hormone-resistant prostate cancer therapy

MedWire News - Prostate Cancer — Wed, 22 Apr 2009 00:00:00 +0100

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Safety and Efficacy of the Specific Endothelin-A Receptor Antagonist ZD4054 in Patients with Hormone-Resistant Prostate Cancer and Bone Metastases Who Were Pain Free or Mildly Symptomatic: A Double-Blind, Placebo-Controlled, Randomised, Phase 2 Trial

European Urology — Tue, 21 Apr 2009 23:58:24 +0100

Conclusions: The primary end point of time to progression was not achieved in this study, but an improvement was seen in overall survival in both active treatment arms. ZD4054 was well tolerated.Trial registration: Clinicaltrials.gov NCT00090363.Take Home Message: Specific endothelin-A receptor antagonist ZD4054 was associated with a promising improvement in overall survival compared with placebo and was generally well tolerated in patients with pain-free or mildly symptomatic metastatic hormone-resistant prostate cancer. Phase 3 trials are underway. (Source: European Urology)

Does chemotherapy have a role before hormone-resistant disease develops?

Current Urology Reports — Tue, 21 Apr 2009 04:32:42 +0100

Abstract Recent studies have demonstrated a survival benefit for chemotherapy in metastatic hormone-resistant prostate cancer. In other malignancies such as breast or colorectal cancer, use of active chemotherapy regimens earlier in the course of the disease has resulted in improvements in disease-free and overall survival. This review discusses the status of chemotherapy in prostate cancer and addresses evidence regarding the use of chemotherapy in hormone-sensitive disease, alone and in combination with androgen deprivation therapy. Content Type Journal ArticleDOI 10.1007/s11934-009-0038-3Authors James P. DeanCelestia S. Higano, University of Washington, Seattle Cancer Care Alliance Department of Medicine, Division of Medical Oncology and Department of Urology 825 Eas...

Modern chemotherapy strategies for management of ‘Hormone Resistant Prostate Cancer’ (HRPC)—When should the urologist refer?

British Journal of Medical and Surgical Urology — Sat, 18 Apr 2009 16:04:06 +0100

This article addresses many of these practical issues. (Source: British Journal of Medical and Surgical Urology)

Pretreatment frequency of circulating IL-17+CD4+ T-cells, but not Tregs, correlates with clinical response to whole-cell vaccination in prostate cancer patients

International Journal of Cancer — Mon, 06 Apr 2009 23:00:00 +0100

The aim of this study was to determine the prognostic implications of the pretreatment level of Th17 cells compared with regulatory T-cell status in prostate cancer patients receiving active whole cell immunotherapy. Ten-color flow cytometry was used to analyze IL-17-producing CD4+ T-cells in the peripheral blood of hormone-resistant non-bone metastatic prostate cancer patients prior to immunotherapy with an allogeneic whole-cell vaccine. Surface expression of the chemokine receptors CCR4 and CCR6 was used to further subdivide IL-17-producing cells into subsets with distinct homing properties. The frequency of circulating regulatory T-cells (Tregs), defined as CD3+CD4+CD127loFoxp3+CD25+ was compared in the same patients. The frequency of CCR4-IL-17+CD4+ T-cells prevaccination inversely cor...

A Novel Androgen Receptor Splice Variant Is Up-regulated during Prostate Cancer Progression and Promotes Androgen Depletion-Resistant Growth

Cancer Research — Tue, 17 Mar 2009 04:00:00 +0100

The androgen receptor (AR) plays a key role in progression to incurable androgen ablation–resistant prostate cancer (PCA). We have identified three novel AR splice variants lacking the ligand-binding domain (designated as AR3, AR4, and AR5) in hormone-insensitive PCA cells. AR3, one of the major splice variants expressed in human prostate tissues, is constitutively active, and its transcriptional activity is not regulated by androgens or antiandrogens. Immunohistochemistry analysis on tissue microarrays containing 429 human prostate tissue samples shows that AR3 is significantly up-regulated during PCA progression and AR3 expression level is correlated with the risk of tumor recurrence after radical prostatectomy. Overexpression of AR3 confers ablation-independent growth of PCA cells...

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A 16-year clinical experience with intermittent androgen deprivation for prostate cancer: oncological results

World Journal of Urology — Fri, 27 Feb 2009 13:52:23 +0100

Conclusions Intermittent androgen deprivation is an acceptable treatment in different stages of PC. Duration of cycle decreased progressively during therapy. Age, Gleason score and PSA are factors predicting mortality. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00345-009-0393-1Authors Dominique Prapotnich, Université Paris Descartes Department of Urology, Institut Mutualiste Montsouris 42 Boulevard Jourdan 75014 Paris cedex FranceXavier Cathelineau, Université Paris Descartes Department of Urology, Institut Mutualiste Montsouris 42 Boulevard Jourdan 75014 Paris cedex FranceFrançois Rozet, Université Paris Descartes Department of Urology, Institut Mutualiste Montsouris 42 Boulevard Jourdan 75014 Paris cedex FranceEric Barret, Université Paris...

CTCs predict hormone-resistant prostate cancer survival

MedWire News - Oncology — Thu, 12 Feb 2009 00:00:00 +0100

Circulating tumor cell numbers should be measured in men entering clinical trials for advanced metastatic prostate cancer, suggest researchers who say the marker should be used as a continuous variable. (Source: MedWire News - Oncology)

CTCs predict hormone-resistant prostate cancer survival

MedWire News - Prostate Cancer — Thu, 12 Feb 2009 00:00:00 +0100

Circulating tumor cells as a potential efficacy end point in clinical trials of hormone-resistant prostate cancer

Current Urology Reports — Sun, 11 Jan 2009 06:43:54 +0100

Content Type Journal ArticleCategory Clinical Trials ReportDOI 10.1007/s11934-009-0002-2Authors Samir S. Taneja Journal Current Urology ReportsOnline ISSN 1534-6285Print ISSN 1527-2737 Journal Volume Volume 10 Journal Issue Volume 10, Number 1 / January, 2009 (Source: Current Urology Reports)

Phase II Study Shows That ZD4054 Could Improve Survival For Hormone Resistant Prostate Cancer (HRPC) Patients With Bone Metastases

Cancer / Oncology News From Medical News Today — Wed, 03 Dec 2008 09:00:00 +0100

A novel compound in development by AstraZeneca as an oral tablet for hormone resistant prostate cancer (HRPC), ZD4054, could improve overall survival (OS) in men with metastatic HRPC, according to Phase II data published today in European Urology.[1] Men with advanced prostate cancer may receive initially effective treatment with hormonal therapies to which the majority of prostate cancers can later become resistant. (Source: Cancer / Oncology News From Medical News Today)

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Molecular markers in prostate cancer. Part II: potential roles in management.

Asian Journal of Andrology — Mon, 01 Dec 2008 05:00:00 +0100

Authors: Agrawal S, Patil KP, Dunsmuir WD Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities. New molecular markers have emerged as potential diagnostic and prognostic indicators; these were summarized in Part I of this review in the Asian Journal of Andrology. A number of molecular markers are now being used to enhance PCa imaging and staging. However, management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed. Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation. Additionally, markers identified in early PCa and precurs...

Safety and Efficacy of the Specific Endothelin-A Receptor Antagonist ZD4054 in Patients with Hormone-Resistant Prostate Cancer and Bone Metastases Who Were Pain Free or Mildly Symptomatic: A Double-Blind, Placebo-Controlled, Randomised, Phase 2 Trial.

European Urology — Fri, 28 Nov 2008 05:00:00 +0100

CONCLUSIONS: The primary end point of time to progression was not achieved in this study, but an improvement was seen in overall survival in both active treatment arms. ZD4054 was well tolerated. TRIAL REGISTRATION: Clinicaltrials.gov NCT00090363. PMID: 19042080 [PubMed - as supplied by publisher] (Source: European Urology)

Marillion Acquires Exclusive Worldwide Rights To 177Lu-AMBA , A First In Class Targeted Radiotherapeutic For Advanced Prostate Cancer

Cancercompass News: Prostate Cancer — Thu, 13 Nov 2008 07:20:01 +0100

MALVERN, Pa. & PRINCETON, N.J. -- Marillion Pharmaceuticals Inc. and Bracco Imaging S.p.A., one of the world's leading companies in the diagnostic imaging business and part of the Bracco Group, announced today that the two companies have entered into a license agreement granting Marillion exclusive worldwide rights to complete clinical development and to commercialize Bracco's (177)Lu-AMBA for the treatment of hormone-resistant prostate and advanced (metastatic) breast cancers. According to the World Health Organization (WHO), prostate and breast cancers affect more than 4 million patients via new diagnoses each year. Prostate cancer is a chronic disease occurring in men over 50 years old. The cancer evolves in two phas... (Source: Cancercompass News: Prostate Cancer)

Marillion Pharmaceuticals and Bracco Imaging S.p.A. Announce License Agreement to Develop and Commercialize Novel Cancer Treatment : Marillion acquires exclusive worldwide rights to 177Lu-AMBA, a first in class targeted radiotherapeutic for advanced prostate and breast cancers discovered and developed by Bracco Imaging S.p.A.

PRWeb: Medical Pharmaceuticals — Wed, 12 Nov 2008 09:18:59 +0100

Marillion Pharmaceuticals Inc. and Bracco Imaging S.p.A., one of the world’s leading companies in the diagnostic imaging business and part of the Bracco Group, announced today that the two companies have entered into a license agreement granting Marillion exclusive worldwide rights to complete clinical development and to commercialize Bracco’s 177Lu-AMBA for the treatment of hormone-resistant prostate and advanced (metastatic) breast cancers. (PRWeb Nov 11, 2008) Read the full story at http://www.prweb.com/releases/bracco_imaging/bracco_group/prweb1601944.htm (Source: PRWeb: Medical Pharmaceuticals)

Prostate cancer Multidisciplinary approach: a key to success.

Critical Reviews in Oncology Hematology — Fri, 22 Aug 2008 04:00:00 +0100

Authors: Montagut C, Albanell J, Bellmunt J Diagnosis and treatment of prostate cancer has improved in the last few years, in part due to a multidisciplinary approach between urologists, oncologists, radiotherapists, radiologists, pathologists, basic and translational researchers for a successful management. The TAX 327 study is the paradigm of a smooth communication between expert physicians that led to the approval of docetaxel in metastatic hormone-resistant prostate cancer (HRPC). Survival benefit with docetaxel in HRPC was confirmed in an updated survival analysis reported this year. A nomogram to predict survival in metastatic HRPC treated with chemotherapy was established based on the TAX 327 study. Unfortunately in early prostate cancer, some of the phase III clinical trials wi...

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Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line

Journal of Translational Medicine — Fri, 08 Aug 2008 04:00:00 +0100

Conclusion: The zoledronic acid-docetaxel combination produced a highly significant synergistic effect on the LNCaP cell line grown in normal or hormone-deprived medium, the principal molecular mechanisms involved being apoptosis and decreased pMEK and Mcl-1 expression. This experimentally derived schedule would seem to prevent the selection and amplification of hormone-resistant cell clones and could thus be potentially used alongside standard androgen deprivation therapy in the management of hormone-sensitive prostate carcinoma. (Source: Journal of Translational Medicine)

Halozyme Therapeutics Announces Positive Findings With Pegylated Enzyme In Prostate Cancer Models

Cancercompass News: Prostate Cancer — Fri, 01 Aug 2008 05:00:00 +0100

Halozyme Therapeutics, Inc., a biopharmaceutical company developing and commercializing products targeting the extracellular matrix, announced the presentation of positive pre-clinical animal efficacy data for its pegylated-rHuPH20 enzyme (PEGPH20) at the American Association for Cancer Research (AACR) Translational Cancer Medicine meeting in Monterey, CA. The study showed that treatment of hormone resistant human prostate cancer in tumor bearing mouse models with intravenous PEGPH20 in combination with the chemotherapeutic drugs, docetaxel (Taxotere(R)) or liposomal doxorubicin (Doxil(R)) resulted in a substantial increase in anti-tumor activity. The docetaxel combination treatment demonstrated significantly enhanced survival compared to t... (Source: Cancercompass News: Prostate Cancer)

Infinity and MedImmune Announce Approval for Generic Name for Novel Hsp90 Inhibitor

Medical News (via PRIMEZONE) — Mon, 04 Feb 2008 13:03:00 +0100

CAMBRIDGE, Mass. and GAITHERSBURG, Md., Feb. 4, 2008 (PRIME NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) and MedImmune today announced that the United States Adopted Names (USAN) Council, in consultation with the World Health Organization (WHO) International Nonproprietary Names Expert Committee, has approved the use of the nonproprietary or generic name "retaspimycin" for the companies' lead heat shock protein 90 (Hsp90) inhibitor, IPI-504. Retaspimycin hydrochloride is currently being evaluated in clinical trials for the potential treatment of a variety of solid tumor cancers, including gastrointestinal stromal tumors, non-small cell lung cancer, and hormone resistant prostate cancer. (Source: Medical News (via PRIMEZONE))

A docetaxel plus prednisone regimen "remains the preferred treatment option" in most men with metastatic, hormone-resistant prostate cancer

Inpharma — Tue, 29 Jan 2008 07:49:57 +0100

(Source: Inpharma)

Updated survival data from TAX 327 study shows docetaxel plus prednisone superior to mitoxantrone plus prednisone for advanced prostate cancer?

NeLM news - Cancer — Tue, 29 Jan 2008 00:00:00 +0100

According to an updated analysis of the TAX 327 study, treatment of advanced prostate cancer with 3-weekly docetaxel in addition to prednisone resulted in statistically significantly longer survival times compared to treatment with mitoxantrone in combination with prednisone. The TAX 327 study had compared docetaxel administered every 3 weeks (D3), weekly docetaxel (D1), and mitoxantrone (M), each with prednisone (P), in 1,006 men with metastatic hormone-resistant prostate cancer (HRPC). The initial analysis at Aug 2003 when 557 deaths had already occurred, had shown statistically significant better survival and response rates for pain, prostate-specific antigen (PSA), and quality of life for D3P when compared with MP. The updated analysis, performed in March 2007 showed the following re...

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Docetaxel Every Three Weeks Best for Certain Metastatic Prostate Cancers

Medscape Pharmacist Headlines — Mon, 28 Jan 2008 22:41:15 +0100

The survival of patients with hormone-resistant prostate cancer is significantly longer after treatment with docetaxel every 3 weeks with prednisone (D3P) compared with other regimens, according to the follow-up of a major study. Reuters Health Information (Source: Medscape Pharmacist Headlines)

A docetaxel plus prednisone regimen "remains the preferred treatment option" in most men with metastatic, hormone-resistant prostate cancer.

Inpharma Weekly — Sat, 26 Jan 2008 08:35:40 +0100

Page: 12 (Source: Inpharma Weekly)

Down-regulation of androgen-receptor and PSA by phytochemicals.

International Journal of Oncology — Sun, 20 Jan 2008 22:31:12 +0100

This study describes the effects of three of these compounds (oridonin, isoliquiritigenin and wogonin) on cell proliferation, cell apoptosis, cell cycle parameters, AR and PSA protein expression. In each case, these compounds have independent activities which may partly contribute to the biological activity of PC-SPES. PMID: 18202763 [PubMed - in process] (Source: International Journal of Oncology)

Jefferson Scientists Find Protein Potential Drug Target For Treatment-resistant Prostate Cancer

Cancercompass News: Prostate Cancer — Thu, 17 Jan 2008 04:36:00 +0100

PHILADELPHIA -- Scientists at Jefferson Kimmel Cancer Center in Philadelphia have found that a signaling protein that is key to prostate cancer cell growth is turned on in nearly all recurrent prostate cancers that are resistant to hormone therapy. If the findings hold up, the protein, called Stat5, may be a specific drug target against an extremely difficult-to-treat cancer. In addition, the researchers, led by Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology at Jefferson Medical College of Thomas Jefferson University, also showed that the convergence of two biological pathways could be responsible for making such hormone-resistant prostate cancers especially dangerous. They have found that a synergy between Stat5 an... (Source: Cancercompass News: Prostate Cancer)

[Genitourinary Cancer] Docetaxel Plus Prednisone or Mitoxantrone Plus Prednisone for Advanced Prostate Cancer: Updated Survival in the TAX 327 Study

Journal of Clinical Oncology — Tue, 08 Jan 2008 05:00:00 +0100

Conclusion The present analysis confirms that survival of men with metastatic HRPC is significantly longer after treatment with D3P than with MP. Consistent results are observed across subgroups of patients. (Source: Journal of Clinical Oncology)

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[Chemotherapy for prostate cancer.]

Presse Medicale — Wed, 19 Dec 2007 05:00:00 +0100

Authors: Medioni J, Dionysopoulos D, Banu E, Scotté F, Beuzeboc P, Oudard S Chemotherapy treatment for patients with prostate cancer has advanced considerably during the past decade. The first demonstration of the efficacy of palliative chemotherapy in patients with hormone-resistant prostate cancer was followed by FDA approval of mitoxantrone in this setting and by studies showing the usefulness of several different drugs in these patients. Docetaxel became the standard treatment for them. The development of new cytotoxic molecules and targeted therapies as well as the evaluation of the efficacy of docetaxel in earlier stages of prostate cancer, with many ongoing studies, are the current lines of research for improving management of these hormone-refractory patients. PMID: 18...

The androgen receptor as putative therapeutic target in hormone-refractory prostate cancer.

Recent Patents on Anti-Cancer Drug Discovery — Thu, 01 Nov 2007 04:00:00 +0100

Authors: Kageyama Y, Hyochi N, Kihara K, Sugiyama H The androgen receptor (AR) plays a central role in the initiation and growth of prostate cancer. Androgen deprivation therapy (ADT) has been a gold standard for advanced prostate cancer for decades. Unfortunately, suppressive effects of ADT do not last long and hormone-refractory prostate cancer develops within several years. In spite of extensive research on mechanisms of hormone-independent growth of prostate cancer, there are few effective treatment options for recurrent tumors and most patients die from the disease in a short period of time. Accumulating evidence suggests that the AR signaling system remains intact and activated despite low levels of androgens in hormone-resistant prostate cancer. Currently, modifications to the A...

Transcriptional Regulation of Human Protease-Activated Receptor 1: A Role for the Early Growth Response-1 Protein in Prostate Cancer

Cancer Research — Wed, 17 Oct 2007 04:00:00 +0100

Transcriptional regulation plays a central role in the molecular pathways underlying preferential cancer growth and metastasis. In the present study, we investigated the regulation of human protease-activated receptor 1 (hPar1) gene overexpression in the malignant androgen hormone-resistant phase. We found increased hPar1 RNA chain elongation and no change in message stability in cells with high levels of PAR1 expression, indicating that increased transcription is largely responsible for the overexpression of hPar1 in prostate tumor progression. Enforced expression of early growth response-1 (Egr-1) plasmid markedly enhanced luciferase activity driven by the hPar1 promoter. The neuroendocrine peptide bombesin significantly induced hPar1 expression and increased the ability of the cells to ...

A specific endothelin A receptor antagonist, ZD 4054, may increase overall survival among patients with hormone-resistant prostate cancer

Inpharma — Mon, 08 Oct 2007 11:47:29 +0100

(Source: Inpharma)

A specific endothelin A receptor antagonist, ZD 4054, * may increase overall survival among patients with hormone-resistant prostate cancer,.

Inpharma Weekly — Sat, 06 Oct 2007 00:35:58 +0100

Page: 14 (Source: Inpharma Weekly)

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Investigational therapy for hormone-resistant PCa shows survival advantage

UrologyTimes - Prostate Cancer — Tue, 02 Oct 2007 23:43:49 +0100

The investigational compound ZD4054, an endothelin-A receptor antagonist, appears to positively impact overall survival in patients with hormone-resistant prostate cancer, according to the results of a randomized, double-blind, placebo-controlled, phase II study presented at the European Congress of Clinical Oncology in Barcelona. (Source: UrologyTimes - Prostate Cancer)

Efficacy of Low-dose Ketoconazole in Hormone Refractory Prostate Cancer Patients at the National Cancer Centre and The Cancer Institute, Singapore.

Ann Acad Med Singapo... — Mon, 01 Oct 2007 04:00:00 +0100

Conclusions: Low-dose ketoconazole bridges the gap in the continuum of treatment for patients who have failed ADT and in whom cytotoxic chemotherapy would have a significant impact on the quality of life. Its good toxicity profile, low cost and ease of administration makes it a viable option for this group of patients. PMID: 17987231 [PubMed - in process] (Source: Ann Acad Med Singapo...)

Announcing Wide-Ranging ZD4054 Phase III Development Program For Prostate Cancer Treatment

Health News from Medical News Today — Thu, 27 Sep 2007 16:00:00 +0100

New Phase II data presented suggest that ZD4054, a novel compound in development for the treatment of men with Hormone Resistant Prostate Cancer (HRPC), could offer a promising improvement in overall survival in men with metastatic HRPC who were asymptomatic or mildly symptomatic for pain. [click link for full article] (Source: Health News from Medical News Today)

New AstraZeneca compound shows promoise for hormone resistant prostate cancer patients with bone metastases

News-Medical News Feed — Wed, 26 Sep 2007 21:03:00 +0100

New Phase II data suggests that ZD4054, a novel compound in development for the treatment of men with Hormone Resistant Prostate Cancer (HRPC), could offer a promising improvement in overall survival in men with metastatic HRPC who were asymptomatic or mildly symptomatic for pain. (Source: News-Medical News Feed)

Survival data presented from phase II study of hormone-resistant prostate cancer patients

News-Medical News Feed — Wed, 26 Sep 2007 20:01:00 +0100

The results from the randomized, double -blind, placebo -controlled, Phase II EPOC (Endothelin A Proof Of Concept) Study of ZD4054 - a specific endothelin A (ETA) receptor antagonist – were delivered at the 14th European Congress of Clinical Oncology (ECCO, 23-27 September, Barcelona). (Source: News-Medical News Feed)

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ECCO: Investigational Drug Shows Survival Edge in Advanced Prostate Cancer

MedPage Today Public Health — Tue, 25 Sep 2007 21:38:02 +0100

BARCELONA, Spain -- An investigational drug that blocks key cancer growth messages appears to give patients with metastatic hormone resistant prostate cancer an extra six months' survival. (Source: MedPage Today Public Health)

ECCO: Investigational Drug Shows Survival Edge in Advanced Prostate Cancer

ConsultantLive — Tue, 25 Sep 2007 10:38:00 +0100

Astrazeneca To Start Phase III Trials With ZD4054 - A Novel Treatment For Patients With Hormone Resistant Prostate Cancer

Health News from Medical News Today — Sat, 28 Jul 2007 08:00:00 +0100

AstraZeneca announced it will be moving its novel, oral agent ZD4054 into Phase III development in men with hormone resistant prostate cancer - a disease which affects approximately 60,000 new patients in the US alone each year.[i] The Phase III trial programme will begin before the end of 2007. [click link for full article] (Source: Health News from Medical News Today)

Secondary hormonal manipulation of prostate cancer

Current Urology Reports — Tue, 12 Jun 2007 06:36:04 +0100

Abstract Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases develop disease progression. Patients with hormone-resistant prostate cancer (HRPC) have a median survival of approximately 18 months, and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a het...

Circulating Tumor Cells Predict How Prostate Cancer Patients Respond To Chemotherapy

Prostate News From Medical News Today — Fri, 08 Jun 2007 12:00:00 +0100

The number of tumor cells circulating in the bloodstream of patients with metastatic, hormone-resistant, prostate cancer can predict how they will do with chemotherapy, according to results of an international trial. The findings, if backed by larger studies, could have important implications for designing personalized treatments for this very dangerous type of prostate cancer, the researchers say.The team of scientists - including first author Jose Moreno, M.D. [click link for full article] (Source: Prostate News From Medical News Today)

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Trial Shows Circulating Tumor Cells Predict How Prostate Cancer Patients Do With Chemotherapy

ScienceDaily Headlines — Tue, 05 Jun 2007 18:00:00 +0100

The number of tumor cells circulating in the bloodstream of patients with metastatic, hormone-resistant, prostate cancer can predict how they will do with chemotherapy, according to results of an international trial. The findings, if backed by larger studies, could have important implications for designing personalized treatments for this very dangerous type of prostate cancer, says a Jefferson Medical College researcher. (Source: ScienceDaily Headlines)

Updated Study Results Reinforce Survival Benefit of Taxotere(R) (Docetaxel) for Men with Advanced, Hormone-Resistant Prostate Cancer

HSMN NewsFeed — Mon, 04 Jun 2007 23:23:51 +0100

ASCO Oral Presentation Reports Significantly More Patients Treated with Taxotere(R)-Based Chemotherapy Regimen Survived at Least Three Years CHICAGO, June 4 (HSMN NewsFeed) -- Taxotere® (docetaxel) Injection Concentrate-based chemotherapy (Taxoter... Biopharmaceuticals, Oncologysanofi-aventis, Taxotere, docetaxel, prostate cancer (Source: HSMN NewsFeed)

The role of androgen in determining differentiation and regulation of androgen receptor expression in the human prostatic epithelium transient amplifying population

Journal of Cellular Physiology — Thu, 31 May 2007 04:00:00 +0100

Abnormal differentiation in epithelial stem cells or their immediate proliferative progeny, the transiently amplifying population (TAP), may explain malignant pathogenesis in the human prostate. These models are of particular importance as differing sensitivities to androgen among epithelial cell subpopulations during differentiation are recognised and may account for progression to androgen independent prostate cancer. Androgens are crucial in driving terminal differentiation and their indirect effects via growth factors from adjacent androgen responsive stroma are becoming better characterised. However, direct effects of androgen on immature cells in the context of a prostate stem cell model have not been investigated in detail and are studied in this work. In [alpha]2[beta]1hi stem cell...

The establishment of two paclitaxel-resistant prostate cancer cell lines and the mechanisms of paclitaxel resistance with two cell lines

The Prostate — Tue, 17 Apr 2007 04:00:00 +0100

Although paclitaxel is used for hormone-resistant prostate cancer, relapse definitely occurs later. Details of the molecular mechanism responsible for paclitaxel- resistance remain unclear.We established paclitaxel-resistant cells, DU145-TxR and PC-3-TxR from parent DU145 and PC-3. To characterize these cells, we examined cross-resistance to other anticancer drugs. Expression of several potential genes that had been related to drug-resistance was compared with parent cells by RT-PCR and Western blotting. Methylation analysis of multiple drug resistance (MDR1) promoter was carried out using bisulfite-modified DNA from cell lines. Knockdown experiments using small interfering RNA (siRNA) were also performed to confirm responsibility of drug-resistance. Finally, cDNA microarray was performed ...

Chemotherapy for hormone-resistant prostate cancer: Where are we today?

Indian Journal of Urology — Thu, 25 Jan 2007 06:35:02 +0100

Buchler Tomas, Harland Stephen JIndian Journal of Urology 2007 23(1):55-60Significant progress has been achieved in chemotherapy for hormone-resistant prostate cancer (HRPC) in the last five years. Although the disease was long considered to be chemoresistant, docetaxel-based regimens in particular have been shown to both palliate symptoms and prolong survival in HRPC patients. Docetaxel is now considered the best available chemotherapy for prostate cancer progressing on first-line hormonal treatment. Other cytotoxics including mitoxantrone, anthracyclines, vinorelbin and vinblastine can alleviate symptoms and improve progression-free survival in HRPC without affecting overall survival. The survival benefit from chemotherapy seen in randomized studies has been small or nonexistent. Results...

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Treatment algorithm in hormone-resistant prostate cancer: Practical guidelines

Indian Journal of Urology — Thu, 25 Jan 2007 06:35:02 +0100

Khochikar Makarand VIndian Journal of Urology 2007 23(1):67-69Treatment of hormone-resistant prostate cancer can be a challenging situation. The first important step in treating this condition is to assess if one has achieved the castrate level or not. If the castrate levels are not achieved, attempt should be made to achieve so. If the castrate level is achieved, then androgen withdrawals may be of help. Supportive care, care of the clinical problems forms an integral part of the treatment. Cancer-specific chemotherapy is certainly an option in progressive disease. (Source: Indian Journal of Urology)

New treatment modalities for hormone-resistant prostate cancer.

Clinical Prostate Cancer — Sat, 06 Jan 2007 21:42:06 +0100

Authors: Lee D PMID: 15046687 [PubMed - indexed for MEDLINE] (Source: Clinical Prostate Cancer)

Biweekly administration of low-dose docetaxel in hormone-resistant prostate cancer: pilot study of an effective subtoxic therapy.

Clinical Prostate Cancer — Sat, 06 Jan 2007 21:42:06 +0100

Authors: Karavasilis V, Briasoulis E, Siarabi O, Pavlidis N Taxane-based chemotherapy has shown activity but also toxicity when administered at standard doses in patients with hormone-resistant prostate cancer (HRPC). In this pilot study, we investigated biweekly low-dose docetaxel in patients with HRPC as a convenient regimen with low toxicity. Sixteen patients with metastatic HRPC entered the study. Median age was 73 years, median performance status (PS) was 2, and median Gleason score was 9. All patients had undergone and failed combined androgen-blockade therapy (luteinizing hormone-releasing hormone analogue plus antiandrogen) for their metastatic disease; 3 had also been treated with mitoxantrone. Treatment consisted of docetaxel 30 mg/m2 administered every 2 weeks. Prostate-spec...

Elevated E2F1 Inhibits Transcription of the Androgen Receptor in Metastatic Hormone-Resistant Prostate Cancer

Cancer Research — Mon, 18 Dec 2006 07:00:00 +0100

In this study, we examined the expression of E2F1 in 667 prostate tissue cores and compared it with the expression of the androgen receptor (AR), a marker of prostate epithelial differentiation, using tissue microarray analysis. We show that E2F1 expression is low in benign and localized prostate cancer, modestly elevated in metastatic lymph nodes from hormone-naïve patients, and significantly elevated in metastatic tissues from hormone-resistant prostate cancer patients (P = 0.0006). In contrast, strong AR expression was detected in benign prostate (83%), localized prostate cancer (100%), and lymph node metastasis (80%), but decreased to 40% in metastatic hormone-resistant prostate cancer (P = 0.004). Semiquantitative reverse transcription-PCR analysis showed elevated E2F1 mRNA level...

Targeting metastatic prostate cancer: the search for innovative systemic therapies.

Oncology (Williston Park, N.Y.) — Fri, 01 Dec 2006 05:00:00 +0100

This article will provide an overview of targeted or innovative therapies in the treatment of prostate cancer. PMID: 17263128 [PubMed - indexed for MEDLINE] (Source: Oncology (Williston Park, N.Y.))

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Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells.

Braz J Med Biol Res — Wed, 01 Nov 2006 22:13:02 +0100

The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD), specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. Gamma-IR treatment had a significant (P < 0.001) antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose ...

[Original articles] Topoisomerase II-{alpha} expression increases with increasing Gleason score and with hormone insensitivity in prostate carcinoma

Journal of Clinical Pathology — Tue, 27 Jun 2006 06:00:00 +0100

Conclusion: Topoisomerase II- expression was found to increase with the known prognostic marker Gleason score and with hormone insensitivity. Objective evidence is provided for clinical trials with drugs targeting topoisomerase II- to be targeted to patients with prostate cancers of Gleason Score >6 and, in particular, prostate cancers of Gleason Scores 8–10. (Source: Journal of Clinical Pathology)

Docetaxel clears another hurdle in high-risk prostate cancer trials

UrologyTimes - Prostate Cancer — Sat, 20 May 2006 06:00:00 +0100

San Antonio--The foundation for a wider application of docetaxel (Taxotere) in prostate cancer is being laid, but it is far from complete. Two major studies appearing last year allowed the drug to replace mitoxantrone (Novantrone) as a first-line treatment in hormone-resistant metastatic prostate cancer. Data from a continuing phase II study of the agent as adjuvant therapy in radical prostatectomy patients at high risk of recurrence were presented here at the AUA annual meeting. Initial findings have shown that the drug is well tolerated, with reversible side effects. (Source: UrologyTimes - Prostate Cancer)

Mechanisms leading to the development of hormone-resistant prostate cancer.

The Urologic Clinics of North America — Sun, 14 May 2006 06:00:00 +0100

This article focuses on the mechanisms by which hormone resistance develops, including the reactivation of androgen receptor during androgen deprivation therapy, the role of cancer stem cells, and the emergence of epithelial-mesenchymal transition cells, which have increased metastatic potential. It is through an enhanced understanding of these mechanisms that new therapies can be developed to combat this disease. PMID: 16631458 [PubMed - indexed for MEDLINE] (Source: The Urologic Clinics of North America)