Effect of Aerobic Exercise on Genomic Signatures of Prostate Cancer Prognosis

有氧运动对前列腺癌预后基因组特征的影响

基本信息

批准号：
8615849
负责人：
JUNE ML CHAN
金额：
$ 66.28万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-14 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8615849
关键词：
Address Adherence Adoption Adverse effects Aerobic Exercise Affect Anxiety Base Excision Repairs Biological Biology Biopsy California Cancer Biology Cancer Prognosis Cancer Survivor Cessation of life Clinical Comorbidity Control Groups DNA Repair DNA Repair Pathway Data Development Diagnosis Disease Disease Progression Erectile dysfunction Exercise Future Gene Expression Genomics Gleason Grade for Prostate Cancer Goals Grant Growth Factor Home environment Human Incontinence Indolent Lead Longitudinal Studies Malignant Neoplasms Malignant neoplasm of prostate Messenger RNA Mitogen-Activated Protein Kinase 14 Mus Neoplasm Metastasis Normal tissue morphology Outcome Pathologic Pathway interactions Pattern Phase III Clinical Trials Phenotype Phosphatidylinositols Phosphotransferases Physical activity Plasma Probability Prognostic Marker Prostate Prostate Cancer therapy Prostate-Specific Antigen Prostatic Neoplasms Protocols documentation Public Health RNA Radiosurgery Randomized Controlled Trials Recommendation Reporting Research Risk San Francisco Signal Pathway Signal Transduction Staging Stress Testing Time Tissues Toxic effect Tumor Tissue United States Universities Vascular Endothelial Growth Factors Vascularization Walking Work adverse outcome angiogenesis arm base cancer diagnosis cohort disorder risk fitness follow-up high risk improved lifestyle intervention mRNA Expression men novel post intervention programs psychosocial public health priorities public health relevance treatment as usual tumor tumor progression

项目摘要

Title: Effect of Aerobic Exercise on Genomic Signatures of Prostate Cancer Prognosis: 7. PROJECT SUMMARY/ABSTRACT: Prostate cancer is the most commonly diagnosed cancer among men in the United States with more than 241,000 new diagnoses in 2012. Nearly half of the men diagnosed have early stage, low-grade disease, and may be good candidates for active surveillance (AS). AS is an important management option because it reduces overtreatment, including the serious side effects (e.g., incontinence, erectile dysfunction) of standard prostate cancer therapies. However, AS is under-utilized because current clinical tests are imperfect at discerning indolent from aggressive prostate cancer. Furthermore, approximately 15% of men who initially opt for AS ultimately seek curative treatment in the absence of biological progression, due to the anxiety and stress of knowing they have cancer. Hence, identifying strategies that reduce risk of prostate cancer progression and allay AS-specific anxiety could greatly reduce the overtreatment of low risk prostate cancer and benefit public health. We reported that vigorous physical activity and brisk walking after prostate cancer diagnosis were associated with ~60% reductions in prostate cancer progression or death in two distinct cohorts of men with prostate cancer. While compelling, these studies do not address if increasing aerobic exercise after diagnosis favorably alters prostate cancer biology. Our group and others have identified and validated novel prostate genomic signatures that predict poor clinical outcomes among men with low risk prostate cancer, and demonstrated that gene expression in the prostate is modified by short-term lifestyle interventions. Thus, we propose to conduct a randomized controlled trial to evaluate whether 24 weeks of supervised aerobic exercise vs. usual care affects the expression of three validated prostate genomic signatures among 120 men with prostate cancer on AS at the University of California, San Francisco and Duke University. Men assigned to the exercise arm will participate in an individually tailored treadmill-walking program that includes five 30- 45 minute sessions per week at 50-80% of baseline cardiorespiratory fitness (three supervised, two at home). We will also examine the global effects of aerobic exercise on mRNA expression of cancer-related pathways in tumor and normal tissue (e.g. growth factor signaling, angiogenesis, DNA repair); and whether aerobic exercise reduces AS-related anxiety and overall stress compared to usual care. The AS protocol of regular prostate biopsies provides a unique opportunity to study the longitudinal effects of aerobic exercise on prostate cancer biology. The results of this randomized controlled trial will provide the essential evidence needed to support a definitive phase III clinical trial of exercise and prostate cancer progression.

标题：有氧运动对前列腺癌预后基因组特征的影响： 7. 项目概要/摘要：前列腺癌是美国男性中最常诊断出的癌症，患有超过 2012 年新增确诊病例 241,000 例。近一半的确诊男性患有早期、低度疾病，可能是主动监测（AS）的良好候选者。 AS 是一个重要的管理选项，因为它减少过度治疗，包括标准治疗的严重副作用（例如失禁、勃起功能障碍）前列腺癌治疗。然而，由于目前的临床测试不完善，AS 并未得到充分利用。区分惰性前列腺癌和侵袭性前列腺癌。此外，大约 15% 的男性最初由于焦虑和焦虑，选择 AS 最终在没有生物进展的情况下寻求治愈性治疗知道自己患有癌症的压力。因此，确定降低前列腺癌风险的策略进展和缓解 AS 特异性焦虑可以大大减少低风险前列腺癌的过度治疗并有利于公众健康。我们报道前列腺癌后剧烈的体力活动和快走在两个不同队列中，诊断与前列腺癌进展或死亡减少约 60% 相关患有前列腺癌的男性。这些研究虽然令人信服，但并没有解决在运动后是否增加有氧运动的问题。诊断有利于改变前列腺癌的生物学特性。我们的团队和其他人已经识别并验证了新颖的前列腺基因组特征可预测低风险前列腺癌男性的不良临床结果，以及证明短期生活方式干预可以改变前列腺的基因表达。因此，我们提议进行一项随机对照试验，以评估 24 周的监督有氧运动是否有效运动与常规护理会影响 120 名男性中三种经过验证的前列腺基因组特征的表达加利福尼亚大学旧金山分校和杜克大学的 AS 前列腺癌患者。男性分配锻炼手臂将参加单独定制的跑步机行走计划，其中包括 5 次 30- 每周 45 分钟，达到基线心肺健康水平的 50-80%（三场有人监督，两场在家）。我们还将研究有氧运动对癌症相关通路 mRNA 表达的整体影响肿瘤和正常组织（例如生长因子信号传导、血管生成、DNA 修复）；以及是否有氧与常规护理相比，运动可减少与 AS 相关的焦虑和整体压力。常规AS协议前列腺活检提供了一个独特的机会来研究有氧运动的纵向影响前列腺癌生物学。这项随机对照试验的结果将提供必要的证据需要支持运动和前列腺癌进展的明确的 III 期临床试验。