A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer
A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer
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DOI：
10.6004/jnccn.2016.0003
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发表时间：
2016-01-01
影响因子：
13.4
通讯作者：
Zhu, Jingchun
中科院分区：
文献类型：
--
作者：
Blau, C. Anthony;Ramirez, Arturo B.;Zhu, Jingchun
加速癌症研究预计需要新型的临床试验。本报告描述了组学在癌症中的强化试验（ITOMIC）和一名三阴性乳腺癌转移到骨的参与者，他的循环肿瘤细胞（ctc）明显升高，在9个月内监测了48次。共有来自14家机构的32名研究人员参与了患者的评估；20名研究人员之前没有参与过患者护理，其中18名是专门为该患者招募的。3个骨髓样本的全外显子组测序显示了一种新的ROS1变异，估计存在于大多数或所有肿瘤细胞中。在对顺铂的初步反应后，克唑替尼敏感性的假设被推翻。白细胞分离后的部分CTC富集允许开发差异高通量药物筛选，并显示出对正在研究的BCL-2的bh3模拟抑制剂的敏感性，由于制药赞助商的要求被拒绝，无法在患者中进行测试。CTC簇的数量和大小与临床状况和最终死亡相关。集中分布的研究人员网络的专业知识，集中监测癌症患者，可以产生癌症自然历史的高分辨率视图，并为治疗提供新的机会。优化需要获得研究药物。
Accelerating cancer research is expected to require new types of clinical trials. This report describes the Intensive Trial of OMics in Cancer (ITOMIC) and a participant with triple-negative breast cancer metastatic to bone, who had markedly elevated circulating tumor cells (CTCs) that were monitored 48 times over 9 months. A total of 32 researchers from 14 institutions were engaged in the patient's evaluation; 20 researchers had no prior involvement in patient care and 18 were recruited specifically for this patient. Whole-exome sequencing of 3 bone marrow samples demonstrated a novel ROS1 variant that was estimated to be present in most or all tumor cells. After an initial response to cisplatin, a hypothesis of crizotinib sensitivity was disproven. Leukapheresis followed by partial CTC enrichment allowed for the development of a differential high-throughput drug screen and demonstrated sensitivity to investigational BH3-mimetic inhibitors of BCL-2 that could not be tested in the patient because requests to the pharmaceutical sponsors were denied. The number and size of CTC clusters correlated with clinical status and eventually death. Focusing the expertise of a distributed network of investigators on an intensively monitored patient with cancer can generate high-resolution views of the natural history of cancer and suggest new opportunities for therapy. Optimization requires access to investigational drugs.