Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine.
Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine.
复制标题
DOI：
10.1158/2159-8290.cd-16-1154
复制
发表时间：
2017-05
期刊：
影响因子：
28.2
通讯作者：
Rubin MA
中科院分区：
文献类型：
--
作者：
Pauli C;Hopkins BD;Prandi D;Shaw R;Fedrizzi T;Sboner A;Sailer V;Augello M;Puca L;Rosati R;McNary TJ;Churakova Y;Cheung C;Triscott J;Pisapia D;Rao R;Mosquera JM;Robinson B;Faltas BM;Emerling BE;Gadi VK;Bernard B;Elemento O;Beltran H;Demichelis F;Kemp CJ;Grandori C;Cantley LC;Rubin MA
精密医学是一种考虑到个人基因、环境和生活方式暴露的影响来量身定做干预措施的方法。在这里，我们描述了一个强大的精密癌症护理平台的开发，它集成了整个外显子组测序(WES)和一个活的生物库，使得能够在患者来源的肿瘤有机化合物上进行高通量药物筛选。迄今为止，在IRB批准的临床试验中，已经从769名患者中建立了56种肿瘤来源的器官培养和19种患者来源的异种移植(PDX)模型。由于仅靠基因组学不足以确定大多数晚期疾病患者的治疗方案，我们使用了高通量药物筛选有效策略。对四个病例，两个子宫恶性肿瘤和两个结肠癌的肿瘤来源细胞的分析，确定了有效的药物和药物组合，随后使用3D培养和PDX模型进行了验证。该平台因此促进了可在临床试验中评估的新治疗方法的发现，并为已用尽标准临床选择的个别患者提供个性化治疗选择。
Precision Medicine is an approach that takes into account the influence of individuals' genes, environment and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform, which integrates whole exome sequencing (WES) with a living biobank that enables high throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures, and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an IRB approved clinical trial. Because genomics alone was insufficient to identify therapeutic options for the majority of patients with advanced disease, we used high throughput drug screening effective strategies. Analysis of tumor derived cells from four cases, two uterine malignancies and two colon cancers, identified effective drugs and drug combinations that were subsequently validated using 3D cultures and PDX models. This platform thereby promotes the discovery of novel therapeutic approaches that can be assessed in clinical trials and provides personalized therapeutic options for individual patients where standard clinical options have been exhausted.