Discovery of Tumor and Treatment Response Biomarkers

作为一名执业放射肿瘤学家，我试图将我的实验室和临床工作整合到一个有凝聚力的转化研究项目中，我把我的临床实践集中在转移性癌症患者的护理上，对他们来说，放射可能是有益的。这些放射治疗是在NIH的护理环境中提供的，通常包括某种形式的免疫定向治疗。这些患者数量庞大，在过去两年中，这些患者占美国国立卫生研究院放射肿瘤科治疗的所有患者的近三分之一。为了更好地确定液体活检或生物流体生物标志物与治疗反应的相关性，该项目的转化研究工作采用了双管齐下的方法：1)与NIH的医学和外科肿瘤学同事合作，研究ev作为肿瘤状态的生物标志物，作为这些合作者现有方案的一部分；2)制定新的临床方案，以更有凝聚力和信息丰富的方式从这一患者群体中获取信息和样本。这两种方法都得到了CCR临床转化任务的支持，并为转化纳米生物学部门正在进行的EV谱研究的基础科学工作提供了支持。整个项目都是在为患者提供最佳护理的背景下产生的，无论是标准护理还是临床试验，同时寻求更好的方法来为个体患者量身定制护理。这一努力导致了一些临床试验的发表（与Tim Greten一起进行的两项用于治疗胃肠道恶性肿瘤的放射和免疫治疗临床试验），另外几项临床试验（与Dickran Kazandjian， Andrea Apolo等人）正在进行中，以及将在来年提交CCR审查的其他多项新临床试验的开发。

As a practicing radiation oncologist, seeking to integrate my laboratory and clinical efforts into a cohesive translational research program, I have focused my clinical practice on the care of patients with metastatic cancers, for whom radiation may be beneficial. These radiation treatments are provided in the setting of their care at NIH, which often includes treatment with some form of immune-directed therapy. This patient population is size-able, and these patients comprised nearly one third of all of the patients treated in the NIH Radiation Oncology Branch across the past two years. To best be able to determine what liquid biopsy or biofluid biomarkers correlate with responses to treatment, the translational research efforts of this project are following a two-pronged approach: 1) collaborating with medical and surgical oncology colleagues at NIH to investigate EVs as biomarkers for tumor status as part of those collaborators' existing protocols, and 2) developing new clinical protocols to capture information and samples from this patient population in a more cohesive and informative manner. Both of these approaches are supported by and provide support to the CCR's clinical translational mission and the basic scientific work ongoing in the Translational Nanobiology Section for the study of EV repertoires. The entirety of this project arises in the context of providing best available care to our patients, whether standard of care or on clinical trial, while seeking to identify better ways to tailor care for individual patients. This effort has led to publication of a number of clinical trials (two clinical trials of radiation and immunotherapy for the treatment of GI malignancies with Tim Greten), ongoing progress of several additional clinical trials (with Dickran Kazandjian, Andrea Apolo, and others), and the development of multiple additional new clinical trials that will be submitted for CCR review in the upcoming year.