AR signaling in Hormone Refractory Prostate Cancer

激素难治性前列腺癌中的 AR 信号传导

• 批准号: 6683441
• 负责人: Jacek Pinski
• 金额: $ 8.1万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6683441
• 关键词: androgen receptor; androgens; athymic mouse; gene expression; gene mutation; hormone regulation /control mechanism; hormone related neoplasm /cancer; hormone sensitivity /resistance; hormone therapy; human tissue; immunocytochemistry; male; neoplasm /cancer chemotherapy; neoplasm /cancer therapy; neoplastic process; nucleic acid sequence; patient oriented research; prognosis; prostate neoplasms; prostate specific antigen; prostate surgery; protooncogene; transcription factor

DESCRIPTION (provided by applicant): The androgen receptor (AR) mediates androgen signaling in the prostate and plays a vital role during all phases of prostate cancer development including the final androgen-independent phases. Somatic AR mutations, increased AR expression, increased AR coactivator expression and/or AR androgen-independent activity are all potential mechanisms causing prostate cancer progression to androgen-independent disease. Such aberrant AR activities might affect and/or predict time to hormone ablation therapy failure. Since clinical practice at present does not consider these mechanisms in choice or timing of treatment, we propose the use of aggressive chemotherapy and/or alternative androgen ablation treatments in conjunction with knowledge of the underlying mechanism of failure. We propose that response to chemo- or alternative hormone ablation therapy will be affected by the underlying AR mechanism of the original ablation therapy failure. In specific aim #1, we will measure AR mutations and expression levels of AR, p160 coactivators and HER2 in archival tissue from men in cohorts representing different stages of disease. In specific aim #2, we intend to do a preclinical trial using the CWR22 tumor model in mice to test early therapy and how it relates to the particular molecular abnormality biologically selected for during the course of androgen ablation treatment. Overall our work will provide a molecular framework of hormone resistant prostate cancer, important indices of prognosis, and the basis for several future clinical trials in alternative treatment strategies of androgen-independent prostate cancer.

描述（由申请人提供）：