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

基本信息

批准号：
9981676
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
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9981676
关键词：
Aftercare Attention Biological Biological Assay Biology Blood Blood specimen Cancer Patient Cell Count Cellular Assay 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 Epithelium 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 effectiveness testing fractionated radiation 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 side effect targeted agent targeted treatment treatment choice tumor tumor progression

项目摘要

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.

接受治疗的患者的循环肿瘤细胞分析和分子谱分析放射治疗抽象的我们建议开发一种具有独特功能和功效的循环肿瘤细胞（CTC）检测方法优于目前可用的 CTC 检测方法最近引起了人们的强烈关注。因为有可能以最小的风险连续研究实体瘤的生物学特性。获得的结果信息，包括预测对目标的反应的遗传信息治疗，可以为接受放射治疗（RT）的患者的临床管理提供信息，从而我们建议以以前无法实现的方式研究非小细胞。肺癌（NSCLC）和黑色素瘤，这两种具有战略重要性的实体瘤，我们对此这些疾病部位代表了放疗的高度优先权。我们的研究性临床试验中的治疗方法并代表每个上皮细胞的例子我们已经获得了初步数据，表明我们的方法。成功检测到目前 FDA 批准的 CTC 检测适用的患者的 CTC 关于 CTC 分析的关键问题仍然存在，这些问题的答案将提供信息。如何最好地将这些测定纳入标准放射肿瘤学实践。问题包括：（1）能否在一系列接受放射治疗的实体瘤中检测到 CTC？ (2) CTC 计数是否可以提前通知疾病？ (3) 所识别的 CTC 的遗传背景是否可以确定？已阐明，它会随着时间和治疗后发生变化吗？我们将采用 CTC 检测吗？这种方法依赖于几乎所有肿瘤中端粒酶活性的升高，这是癌症的一个标志，这是由于缺乏肿瘤标志物的表面表达而造成的不可渗透的限制。具体目标 1 我们将跟踪具有一系列局部表现的患者的 CTC 计数接受 RT 的 NSCLC 测试 CTC 分析是否可以提前通知肿瘤目标 2 将测试 CTC 分析对于接受黑色素瘤治疗的患者是否有效。治疗，包括放射治疗和免疫治疗对于目标3，我们将测试是否遗传。治疗后 CTC 的变化，包括预测治疗反应的 DNA 突变我们成功实现这些科学目标将是生物靶向制剂。阐明 CTC 检测对于接受放疗和放疗的广泛患者的潜在用途其他抗癌治疗。