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：
9243994
负责人：
JUNE ML CHAN
金额：
$ 62.78万
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 2020-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9243994
关键词：
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 Evaluation Exercise Future Gene Expression Genomics Gleason Grade for Prostate Cancer Goals Grant Growth Factor Home environment Human Incontinence Individual Indolent Lead Longitudinal Studies MAPK14 gene Malignant Neoplasms Malignant neoplasm of prostate Messenger RNA Mus Neoplasm Metastasis Normal tissue morphology Operative Surgical Procedures Outcome Pathologic Pathway Analysis 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 Radiation Randomized Controlled Trials Recommendation Reporting Research Risk San Francisco Signal Pathway Signal Transduction Strenuous Exercise Stress Supervision Surveys Testing Time Tissues Toxic effect Tumor Tissue United States Universities Vascular Endothelial Growth Factors Vascularization Walking Work adverse outcome angiogenesis arm base cancer diagnosis cardiorespiratory fitness cohort curative treatments disorder risk follow-up genomic signature high risk improved lifestyle intervention mRNA Expression men novel post intervention predictive signature prostate biopsy prostate cancer model psychosocial public health priorities public health relevance treadmill treatment as usual tumor tumor progression walking program

项目摘要

DESCRIPTION (provided by applicant): 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 o exercise and prostate cancer progression.

描述（由申请人提供）：前列腺癌是美国男性中最常诊断出的癌症，2012 年新诊断出超过 241,000 例。近一半的诊断男性患有早期、低度疾病，可能是良好的候选者用于主动监视（AS）。 AS 是一种重要的治疗选择，因为它可以减少过度治疗，包括标准前列腺癌治疗的严重副作用（例如失禁、勃起功能障碍）。然而，AS 并未得到充分利用，因为目前的临床测试在区分惰性前列腺癌和侵袭性前列腺癌方面并不完善。此外，由于知道自己患有癌症而感到焦虑和压力，大约 15% 最初选择 AS 的男性最终在没有生物进展的情况下寻求治愈性治疗。因此，确定降低前列腺癌进展风险和减轻 AS 特异性焦虑的策略可以大大减少低风险前列腺癌的过度治疗，并有益于公众健康。我们报告说，在前列腺癌诊断后，剧烈的体力活动和快走与两个不同的前列腺癌男性队列的前列腺癌进展或死亡减少约 60% 相关。这些研究虽然令人信服，但并未解决诊断后增加有氧运动是否能有利地改变前列腺癌的生物学特性。我们的小组和其他人已经确定并验证了新的前列腺基因组特征，这些特征可以预测低风险前列腺癌男性的不良临床结果，并证明短期生活方式干预可以改变前列腺中的基因表达。因此，我们建议进行一项随机对照试验，以评估 24 周有监督的有氧运动与常规护理是否会影响加州大学旧金山分校和杜克大学 120 名患有 AS 的前列腺癌男性中三种经过验证的前列腺基因组特征的表达大学。分配到锻炼臂的男性将参加单独定制的跑步机行走计划，其中包括每周 5 次每次 30-45 分钟的训练，达到基线心肺健康的 50-80%（其中 3 次在监督下进行，2 次在家进行）。我们还将研究有氧运动对肿瘤和正常组织中癌症相关途径的 mRNA 表达的整体影响（例如生长因子信号传导、血管生成、DNA 修复）；以及与常规护理相比，有氧运动是否可以减少与 AS 相关的焦虑和整体压力。定期前列腺活检的 AS 方案为研究有氧运动对前列腺癌生物学的纵向影响提供了独特的机会。这项随机对照试验的结果将为支持运动与前列腺癌进展的明确的 III 期临床试验提供必要的证据。