Circulating Tumor Cells Analyses and Molecular Profiling for Patients Receiving Radiation Therapy

接受放射治疗的患者的循环肿瘤细胞分析和分子谱分析

• 批准号: 9304112
• 负责人: JAY FITZGERALD DORSEY
• 金额: $ 43.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9304112
• 关键词: Adverse effects; Aftercare; Attention; Biological; Biological Assay; Biology; Blood; Blood specimen; Cancer Patient; Cell Count; Characteristics; Clinical; Clinical Management; Clinical Protocols; Clinical Trials; Combined Modality Therapy; Complement; DNA Sequence Alteration; Data; Data Collection; Detection; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic radiologic examination; Disease; Effectiveness; Enrollment; Epithelial; FDA approved; Genetic; Genetic Heterogeneity; Genomics; Image; Immunotherapy; Individual; Lead; Lesion; Malignant Neoplasms; Measures; Methods; Molecular Profiling; Monitor; Mutation; Neoplasm Circulating Cells; Non-Small-Cell Lung Carcinoma; Patients; Positron-Emission Tomography; Procedures; Protocols documentation; Radiation; Radiation Oncology; Radiation therapy; Recurrence; Resectable; Risk; Scientific Advances and Accomplishments; Selection for Treatments; Sensitivity and Specificity; Site; Solid Neoplasm; Surface; Techniques; Telomerase; Testing; Therapeutic; Time; Tumor Biology; Tumor Markers; X-Ray Computed Tomography; advanced disease; anticancer treatment; base; cancer cell; chemotherapy; clinical investigation; cohort; genetic information; genetic profiling; imaging modality; improved; individual patient; liquid biopsy; melanoma; minimal risk; neoplastic cell; novel; personalized care; personalized medicine; predicting response; profiles in patients; targeted agent; targeted treatment; treatment choice; tumor; tumor progression

Circulating Tumor Cells Analyses and Molecular Profiling for Patients Receiving Radiation Therapy ABSTRACT We propose to develop a circulating tumor cell (CTC) assay with unique features and efficacy superior to currently available CTC assays. CTC assays have attracted intense recent attention because of the potential to serially interrogate the biology of solid tumors with minimal risk. The resulting information obtained, including genetic information predicting response to targeted therapy, may inform the clinical management of patients receiving radiation therapy (RT), thus “personalizing treatment” in ways previously unachievable. We propose to study non-small cell lung cancer (NSCLC) and melanoma, two solid tumors of strategic importance and for which we have protocols rapidly accruing patients. These disease sites represent high priority for RT treatment in our investigational clinical trials and represent examples of respectively, epithelial and non-epithelial tumors. We have achieved preliminary data that suggests our approach successfully detects CTCs in patients for whom the current FDA-approved CTC assay is ineffective. Key questions regarding CTC analyses remain, the answers to which would inform how best to incorporate these assays into standard radiation oncology practice. These questions include: (1) Can CTCs be detected in a range of solid tumors undergoing radiation therapy (RT) or other forms of treatment? (2) Do CTC counts give lead-time notice of disease recurrence or progression? (3) Can the genetic background of the identified CTCs be elucidated and does it change over time and after treatment? We will employ a CTC detection method that relies on the elevated telomerase activity in almost all tumors, a hallmark of cancer, which is impervious to limitations posed by the lack of surface expression of tumor markers. In Specific Aim 1 we will track CTC counts in patients with a range of presentations of localized NSCLC undergoing RT to test whether CTC analysis can give lead time notice of tumor recurrence. Aim 2 will test whether CTC analysis is effective in melanoma patients undergoing treatment, including radiation and immunotherapy. For Aim 3, we will test whether the genetic profile of CTCs changes after treatment, including DNA mutations that predict for response to biologically targeted agents. Our successful accomplishment of these scientific aims will illuminate the potential usefulness of CTC assays for a wide range of patients receiving RT and other anticancer treatment.

循环的肿瘤细胞分析和接受的患者分子分析 放射治疗 抽象的 我们建议开发具有独特特征并轻松的循环肿瘤细胞（CTC）测定 优于当前可用的CTC分析。 CTC分析引起了最近的关注 因为有可能串行质疑具有最小风险的实体瘤的生物学。这 获得的信息，包括预测对目标的响应的遗传信息 治疗，可以告知接受放射治疗（RT）的患者的临床管理，因此 以前无法实现的方式“个性化治疗”。我们建议研究非小细胞 肺癌（NSCLC）和黑色素瘤，两个具有战略意义的实体瘤，我们为此 具有迅速累积患者的方案。这些疾病部位代表了RT的高优先级 在我们的研究临床试验中的治疗，分别代表上皮的例子 和非上皮肿瘤。我们已经实现了提示我们方法的初步数据 成功检测到当前FDA批准的CTC分析的患者中的CTC 无效。有关CTC分析的关键问题仍然存在，其答案将告知 如何最好地将这些测定纳入标准辐射肿瘤学实践中。这些 问题包括：（1）可以在辐射的一系列实体瘤中检测到CTC 治疗（RT）或其他形式的治疗？ （2）do ctc计数给出疾病的提前时间通知 复发还是进展？ （3）确定的CTC的遗传背景可以 阐明，它会随着时间和治疗后随着时间而变化吗？我们将使用CTC检测 依赖于几乎所有肿瘤的端粒酶活性升高的方法，这是癌症的标志， 这是由于缺乏肿瘤标记表面表达所带来的局限性。在 特定目标1我们将跟踪具有一系列本地化介绍的患者的CTC计数 NSCLC正在进行RT以测试CTC分析是否可以给出肿瘤的提前时间通知 复发。 AIM 2将测试CTC分析是否对正在进行的黑色素瘤患者有效 治疗，包括放射线和免疫疗法。对于AIM 3，我们将测试是否遗传 治疗后CTC的轮廓变化，包括预测对响应的DNA突变 生物靶向剂。我们成功实现这些科学目标将 阐明了CTC分析的潜在有用性，用于接收RT的广泛患者 其他抗癌治疗。