Analysis of the Mechanisms of Actions of Heat Shock Protein (Hsp27) Responsible of the Androgen-independent Evolution in Prostate Cancer

Study Overview
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Brief Summary
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Prostate cancer (PC) represents one of the most common cancers in industrialized countries. Patients with localized disease may be treated with surgery or radiation, while androgen ablation is used as first-line therapy in patients with metastatic disease. While most patients initially respond well to this hormonal therapy, they most ultimately become unresponsive and recur within 2 years as androgen-independent prostate cancer (AIPC). Recently, docetaxel-based regimens have demonstrated improved survival in men with AIPC in two different, large, phase III studies. However, the median overall survival was prolonged for only 2 or 3 months. Androgen independent (AI) progression involves variable combinations of clonal selection, adaptive up-regulation of anti-apoptotic genes, ligand-independent androgen receptor (AR) activation, alternative growth factor pathways, and immune system escape. Additional therapeutic strategies targeting molecular mechanisms mediating resistance, combined with immunotherapy must be developed. One strategy to improve therapies in advanced PC involves targeting genes that are activated by androgen withdrawal, either to delay or prevent the emergence of the resistant AI phenotype. Recently, a scientist,identified Heat Shock Protein (Hsp27) as a highly over-expressed gene in AIPC. Hsp27 knockdown using antisens oligonucleotides (ASO) and small interfering RNA (siRNA) increased apoptotic rates and enhanced hormone- and chemo-therapy in PC. She developed and patented a 2nd generation ASO targeting Hsp27 that has been licensed (investigational drug called OGX-427) and clinical trials phase I/II is currently in process in PC. Despite OGX-427 efficiency, the functional role of stress induced Hsp27 in castration or chemotherapy-induced apoptosis remains undefined. The purpose of this study is to elucidate the pathways leading to Hsp27 action in androgen-independent prostate cancer in order to 1/ Increase the pharmacological safety of OGX-427 and 2/find new specific therapeutic targets and treatment strategy for androgen-independent prostate cancer .

Official Title
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Analysis of the Mechanisms of Actions of Hsp27 Responsible of the Androgen-independent Evolution in Prostate Cancer

Conditions
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Androgen-independent Prostate Cancer

Intervention / Treatment
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* Procedure: Realisation of blood sample, urinary sample and tumor biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prostate adenocarcinoma Patient > 18 years old Patient affiliated to a social security system or benefiting from such a system Signed consent to participate Exclusion Criteria: Patient in emergency situation, major person being the object of a legal protective measure or unable to express its consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: prostate cancer<br>Realisation of blood sample, urinary sample and tumor biopsy | Procedure: Realisation of blood sample, urinary sample and tumor biopsy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Hsp27 protein | Mechanisms of action of Hsp27 protein to elucidate the pathways leading to Hsp27 action in androgen-independent prostate cancer (AIPC) by double hybrid Sos Recruitment System (SRS) | within 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Targets for OGX-427 | Description of new specific therapeutic targets for androgen-independent prostate cancer and pharmacological safety of OGX-427 | within 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Androgen-independent prostate cancer