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

外周血肿瘤细胞分析与分子生物学研究 放射疗法 摘要 我们建议建立一种具有独特功能和有效性的循环肿瘤细胞(CTC)检测方法 优于目前可用的CTC检测方法。CTC检测最近引起了强烈的关注 因为有可能以最小的风险连续询问实体肿瘤的生物学。这个 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，因此 “个性化治疗”，这是以前无法实现的。我们建议研究非小细胞 肺癌(NSCLC)和黑色素瘤，这两种具有战略意义的实体肿瘤，我们 有计划地迅速增加患者。这些疾病部位代表了RT的高度优先级 在我们的研究性临床试验中的治疗，并分别代表上皮性 和非上皮性肿瘤。我们已经获得了初步数据，表明我们的方法 在FDA批准的当前CTC检测方法适用的患者中成功检测到CTC 效果不佳。关于四氯化碳分析的关键问题仍然存在，这些问题的答案将为 如何最好地将这些分析纳入标准的放射肿瘤学实践。这些 问题包括：(1)在接受放射治疗的一系列实体肿瘤中能检测到CTCs吗 治疗(RT)或其他形式的治疗？(2)CTC计数是否提前通知疾病 复发或进展？(3)已鉴定的CTC的遗传背景是否可以 随着时间的推移和治疗后，它是否会发生变化？我们将采用CTC检测 这种方法依赖于几乎所有肿瘤中端粒酶活性的升高，端粒酶是癌症的标志， 它不受缺乏肿瘤标志物表面表达所带来的限制。在……里面 具体目标1我们将跟踪有一系列局限性表现的患者的CTC计数 非小细胞肺癌行RT检查CTC分析能否提前通知肿瘤 复发。Aim 2将测试CTC分析在黑色素瘤患者接受 治疗，包括放射治疗和免疫治疗。对于目标3，我们将测试基因是否 CTCs在治疗后的变化，包括预测疗效的DNA突变 生物靶向剂。我们成功地实现这些科学目标将 阐明CTC检测对接受RT和 其他抗癌治疗。

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.