IGF::OT::IGF PREDICTIVE BIOMARKERS OF PROSTATE CANCER PATIENT SENSITIVITY FOR RADIATION LATE EFFECTS

IGF::OT::IGF 前列腺癌患者对辐射迟发效应的敏感性的预测生物标志物

• 批准号: 9356822
• 负责人: SCOTT GRINDROD, PHD
• 金额: $ 29.95万
• 依托单位: SHUTTLE PHARMACEUTICALS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-19 至 2017-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9356822
• 关键词: Affect; Biological Assay; Biological Markers; Cancer Patient; Capital; Clinical; Clinical Trials; Data; Development; Flare; Injury; Institutional Review Boards; Late Effects; Legal patent; Life; Malignant neoplasm of prostate; Mass Spectrum Analysis; Mediating; Monitor; Outcome; Patients; Pharmacologic Substance; Phase; Plasma; Population; Predisposition; Procedures; Proctitis; Protocols documentation; Quality of life; Radiation; Radiation Tolerance; Radiation Toxicity; Radiation therapy; Reporting; Resolution; Sampling; Small Business Innovation Research Grant; Specimen; Symptoms; Testing; United States National Institutes of Health; Urinary Incontinence; Urinary tract; Validation; Writing; base; biomarker panel; cancer recurrence; clinical application; cohort; commercialization; design; experience; gastrointestinal; metabolomics; predictive marker; product development; radiation response; rectal; urinary

Patients treated for prostate cancer may experience treatment related late effects that adversely affect quality of life and may prove life-threatening. The objective of this Phase I SBIR application is to determine the technical and commercial feasibility of a biomarker panel predictive of radiation mediated late effects in patients treated for prostate cancer. We will develop a metabolite signature of radiation responses in a cohort of patients undergoing stereotactic body radiation therapy (SBRT) for prostate cancer. Analysis of banked plasma samples will be correlated with clinical outcomes to identify markers of urinary and gastrointestinal late effects for validation in a larger clinical population to be proposed in a subsequent Phase II application. The Phase II effort will allow Shuttle Pharmaceuticals to advance its proposed commercialization plan and to raise capital to support validation clinical trials leading to FDA approval. Patients treated with stereotactic body radiation therapy (SBRT) for prostate cancers on an IRB approved protocol have banked clinical specimens and detailed monitoring of quality of life parameters. Sub-sets of these patients have developed urinary incontinence (UI), symptomatic urinary flare (USF), obstructed voiding symptoms/retention (UR) and radiation proctitis (RP). We have used high resolution mass spectrometry based metabolomics/lipidomic profiling to analyze this unique cohort of patient samples and propose here, to leverage our established analytical platform to advance product development and validation of a biomarker panel predictive of radiation toxicities. Metabolites in plasma from a cohort of 100 de-identified patients will be analyzed to develop a kit supporting metabolomic analysis to serve as a biomarker panel predictive of patient susceptibility for radiation late effects.

接受前列腺癌治疗的患者可能会出现治疗相关的晚期效应， 对生活质量产生不利影响，并可能危及生命。本SBIR第I阶段的目标 应用是确定生物标志物小组的技术和商业可行性， 预测接受前列腺癌治疗的患者中放射介导的晚期效应。我们将 在接受放射治疗的患者队列中开发放射反应的代谢物特征， 立体定向放射治疗（SBRT）前列腺癌。库存血浆分析 将样本与临床结果相关联，以确定尿液和 拟在更大的临床人群中验证胃肠道晚期效应， 第二阶段应用。第二阶段的努力将使航天飞机制药公司， 推进其拟议的商业化计划，并筹集资金支持临床验证 FDA批准的临床试验 接受立体定向体部放射治疗（SBRT）治疗前列腺癌的患者 IRB批准的方案已经储存了临床样本，并详细监测了 生命参数这些患者的子集已经发展为尿失禁（UI）， 症状性尿闪（USF）、排尿障碍症状/尿潴留（UR）和放射 直肠炎（RP）。我们使用了基于代谢组学/脂质组学的高分辨率质谱法， 分析这个独特的患者样本队列，并在此提出，利用我们的 建立分析平台，以推进产品开发和生物标志物验证 预测辐射毒性的小组。来自100例去识别队列的血浆中的甲硫氨酸 将对患者进行分析，以开发支持代谢组学分析的试剂盒， 生物标志物组预测患者对辐射迟发效应的易感性。