Molecular Signatures of Lethal an Indolent Prostate Cancer

致命的惰性前列腺癌的分子特征

基本信息

批准号：
7890597
负责人：
PHILIP W KANTOFF
金额：
$ 39.87万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-19 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7890597
关键词：
Address Archives Biochemical Cancer Survivor Cause of Death Cells Cessation of life Clinical Clinical Trials Collaborations Core Biopsy Dana-Farber Cancer Institute Data Set Decision Making Development Diagnosis Diagnostic Disease Epidemiology Failure Formalin Gene Expression Profile Gene Expression Profiling Generations Genes Genomics Goals Health Heterogeneity Hospitals Human Genome Indolent Institutes Institution International Intervention Knowledge Malignant neoplasm of prostate Massachusetts Medical Medicine Methods Molecular Molecular Analysis Molecular Profiling Morbidity - disease rate Natural History Neoplasm Metastasis Operative Surgical Procedures Outcome Paraffin Embedding Patient observation Patients Physicians Process Prostatectomy Public Domains Public Health Schools Radiation Recurrence Reproduction spores Research Personnel Risk Sampling Specimen Sweden Technology Testing Therapeutic Intervention Time Tissue Sample Tissues University Hospitals Woman Work aggressive therapy base cohort follow-up genome-wide men multidisciplinary neoplastic cell new technology novel programs standard of care tumor

项目摘要

One of the main challenges for medicine in the early part of 21st century is to incorporate knowledge of the human genome into the medical management of patients, thereby yielding more precise diagnoses and mechanism-based deployment of therapy. Nowhere is this need more pressing than in the treatment of men with prostate cancer. Prostate cancer is a major cause of death and morbidity, yet large numbers of men are believed to harbor tumors that are indolent even in the absence of therapy. As such, many men receive unnecessary treatment with its attendant effects, and others die of disease despite aggressive therapy. We hypothesize that the variability in the natural history of CaP is determined by heretofore unrecognized molecular heterogeneity of the disease. We therefore propose here to identify a gene expression signature that distinguishes indolent from lethal disease. This Project has 3 Specific Aims: Aim 1: Collect, register, and process archival formalin-fixed paraffin embedded (FFPE) samples from the Swedish Watchful Waiting (WW) cohorts with up to 30 years clinical follow up. Aim 2: Develop molecular signatures of lethal and indolent prostate cancer on the Watchful Waiting FFPE samples using an Illumina expression array platform with over 6000 genes developed specifically for molecular signature discovery. Aim 3: Validate the signatures on Swedish WW cases not used in Aim 2 and test for the presence of these profiles in tumor samples (n=100) from the Physicians' Health Study (PHS). At the conclusion of this proposal, we expect to have discovered and validated molecular predictors of prostate cancer outcome that are appropriate for further clinical development. To accomplish these goals, we have assembled a multidisciplinary team of investigators with a long track record of collaboration, and with particular expertise in the clinical, pathological and epidemiological aspects of prostate cancer, in the development and deployment of genomics technologies, and in advanced computational and statistical analysis.

在21世纪初期，医学的主要挑战之一是将知识纳入人类基因组进入患者的医疗管理，从而产生更精确的诊断和基于机制的治疗部署。没有什么需要比男性的治疗更紧迫的患有前列腺癌。前列腺癌是死亡和发病率的主要原因，但大量男性是据信即使没有治疗，也含有脆弱的肿瘤。因此，许多男人收到不必要的治疗对其随之而来的影响，尽管有积极的疗法，但其他人则死于疾病。我们假设CAP的自然历史上的可变性是由未被认可的迄今为止确定的该疾病的分子异质性。因此，我们在这里建议识别基因表达特征这与致命疾病区分开了。该项目具有3个具体目标：目标1：收集，注册和处理福尔马林固定石蜡嵌入（FFPE）样品中的样品瑞典的注意等待（WW）同伙，最多30年的临床随访。目标2：在注意等待FFPE上发展致命和懒惰前列腺癌的分子特征使用Illumina表达阵列平台的样品，该平台具有超过6000个基因专为专门开发的基因分子签名发现。 AIM 3：验证AIM 2中未使用的瑞典WW案件的签名并测试是否存在医师健康研究（pHS）中肿瘤样品中的剖面（n = 100）。在该提案的结论结束时，我们希望发现并验证了分子预测指标适合进一步临床发育的前列腺癌结果。为了实现这些目标，我们已经组建了一个由合作的长期记录的调查员团队，并与在前列腺癌的临床，病理和流行病学方面的特殊专业知识，基因组技术的开发和部署以及高级计算和统计分析。