Molecular Signatures of Lethal an Indolent Prostate Cancer

致命的惰性前列腺癌的分子特征

• 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
• 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

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.

世纪早期医学面临的主要挑战之一是将 将人类基因组纳入患者的医疗管理，从而产生更精确的诊断， 基于机制的治疗部署。没有什么地方比治疗男性更迫切需要这种治疗 前列腺癌前列腺癌是死亡和发病的主要原因，但大量的男性患有前列腺癌。 据信，这些肿瘤即使在没有治疗的情况下也是惰性的。因此，许多人接受 有些人接受了不必要的治疗，并伴随着其后果，还有一些人尽管接受了积极的治疗，但仍死于疾病。我们 假设CaP自然史的变异性是由迄今未被认识到的 疾病的分子异质性。因此，我们建议在这里确定一个基因表达签名 区分惰性疾病和致命疾病 该项目有三个具体目标： 目的1：收集、登记和处理来自于实验室的福尔马林固定石蜡包埋（FFPE）存档样本。 瑞典观察等待（WW）队列，临床随访长达30年。 目的2：在Watchful Waiting FFPE上开发致死性和惰性前列腺癌的分子特征 样本使用Illumina表达阵列平台，该平台具有超过6000个专门针对 分子特征发现 目标3：验证目标2中未使用的瑞典WW案例上的签名，并测试是否存在这些签名 来自医师健康研究（PHS）的肿瘤样品（n = 100）中的特征。 在这项建议的结论，我们希望已经发现和验证的分子预测， 前列腺癌的结果，适合进一步的临床开发。为了实现这些目标，我们 组建了一个多学科的调查小组，有着长期的合作记录， 在前列腺癌的临床、病理学和流行病学方面， 基因组学技术的开发和部署，以及先进的计算和统计 分析.