Exercise as Interception Therapy in Primary High Risk Cancer

运动作为原发性高危癌症的拦截疗法

• 批准号: 10439860
• 负责人: Luis A Diaz
• 金额: $ 64.44万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-03 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439860
• 关键词: Adherence; Adjuvant; Adjuvant Therapy; Affect; Aftercare; Age; Biological; Breast Cancer Model; Cancer Patient; Cell Proliferation; Cell Survival; Cells; Characteristics; Chronic; Clinic; Clinical; Colorectal Cancer; Data; Development; Diagnosis; Disease; Disease Outcome; Dose; Eligibility Determination; Ensure; Exercise; Exercise Therapy; Exhibits; Exposure to; Financial cost; Future; Grant; Growth Factor; High-Risk Cancer; Home; Immune; Immunologic Surveillance; Inflammatory; Intercept; Investigation; Laboratories; Malignant Neoplasms; Malignant neoplasm of prostate; Medical; Moderate Exercise; Monitor; Mutation; Observational Study; Oncology; Pathway interactions; Patient Outcomes Assessments; Patient Self-Report; Patients; Pharmacodynamics; Phase; Phase Ia Trial; Phenotype; Positive Lymph Node; Primary Neoplasm; Public Health; Recurrence; Recurrent disease; Relapse; Residual Neoplasm; Risk; Safety; Solid Neoplasm; Somatotropin; Strenuous Exercise; Telemedicine; Testing; Time; Toxic effect; Translating; Walking; Work; antitumor effect; appropriate dose; base; cancer cell; cancer risk; cancer type; clinical investigation; cohort; cost; curative treatments; design; drug development; exercise capacity; exercise intensity; exercise intervention; exercise training; experience; experimental study; falls; follow-up; genetic variant; high risk; improved; malignant breast neoplasm; meetings; monocyte; mouse model; novel; oncology trial; peripheral blood; pre-clinical; prevent; primary endpoint; programs; prospective; recruit; relapse risk; screening; standard of care; treadmill; treatment response; tumor; tumor DNA; tumor growth

ABSTRACT Advances in screening and adjuvant therapy have significantly improved disease outcomes in primary (early-stage) cancer, however 30% still experience relapse despite curative treatment. Recurrent (metastatic) disease is currently incurable. Thus, effective strategies to prevent disease recurrence in those patients at highest risk are of major clinical importance. Exercise therapy is a well-tolerated strategy that may also hold significant promise to control MRD in breast, prostate, and colorectal cancer. Observational studies show that self-reported exercise is associated with 20% to 60% reductions in the risk of relapse in primary breast, prostate, and colorectal cancer. Moreover, these observations extend to patients with high-risk (e.g., stage 3, node positive) disease. In preclinical support of these data, we have demonstrated exercise significantly inhibits primary tumor growth in aggressive mouse models of breast, colorectal, and prostate cancer. Finally, we have translated the development of exercise interventions to the clinic with numerous prospective trials demonstrating exercise training is safe, well- tolerated, and exhibits significant pharmacodynamic (PD) activity as illustrated by favorable alterations in the circulating availability of multiple growth factors and hormones as well as inflammatory-immune effectors known to affect cancer cell proliferation and survival in breast, prostate, and colorectal cancer. Collectively, the encouraging data strongly support further clinical investigation of whether exercise has adjuvant therapy benefit in patients with primary solid tumors. We will conduct a phase 1a/1b study of exercise in primary cancer patients at high-risk of disease relapse. We will leverage analysis of circulating tumor DNA (ctDNA) to: (1) identify those at high-risk of relapse, and (2) monitor therapeutic response to exercise. This grant has two specific aims: (1) Aim 1: Phase 1a Dose- Finding and (2) Aim 2: Phase 1b Dose Expansion.

抽象的 筛查和辅助治疗的进步显着改善了原发性疾病的疾病结果 （早期）癌症，然而，尽管进行了治愈性治疗，30% 的癌症仍然会复发。复发性（转移性） 该病目前无法治愈。因此，预防这些患者疾病复发的有效策略 最高风险具有重大临床意义。 运动疗法是一种耐受性良好的策略，也可能对控制 MRD 具有重要意义。 乳腺癌、前列腺癌和结直肠癌。观察性研究表明，自我报告的锻炼与 原发性乳腺癌、前列腺癌和结直肠癌的复发风险降低 20% 至 60%。而且， 这些观察结果适用于患有高风险（例如，第 3 期、淋巴结阳性）疾病的患者。在临床前支持方面 根据这些数据，我们证明运动可以显着抑制攻击性小鼠的原发性肿瘤生长 乳腺癌、结直肠癌和前列腺癌模型。最后我们翻译了exercise的开发 通过大量前瞻性试验对临床进行干预，证明运动训练是安全、良好的 耐受性良好，并表现出显着的药效学 (PD) 活性，如 多种生长因子和激素以及炎症免疫效应物的循环可用性 已知会影响乳腺癌、前列腺癌和结直肠癌的癌细胞增殖和存活。总的来说， 令人鼓舞的数据有力地支持了运动是否具有辅助治疗作用的进一步临床研究 原发性实体瘤患者受益。 我们将对处于疾病高风险的原发性癌症患者进行运动的 1a/1b 期研究 复发。我们将利用循环肿瘤 DNA (ctDNA) 分析来：(1) 识别复发高风险人群， (2) 监测对运动的治疗反应。这笔赠款有两个具体目标：(1) 目标 1：第 1a 阶段剂量- 发现和 (2) 目标 2：1b 阶段剂量扩展。