Pauli Chantal, Hopkins Benjamin D, Prandi Davide, Shaw Reid, Fedrizzi Tarcisio, Sboner Andrea, Sailer Verena, Augello Michael, Puca Loredana, Rosati Rachele, McNary Terra J, Churakova Yelena, Cheung Cynthia, Triscott Joanna, Pisapia David, Rao Rema, Mosquera Juan Miguel, Robinson Brian, Faltas Bishoy M, Emerling Brooke E, Gadi Vijayakrishna K, Bernard Brady, Elemento Olivier, Beltran Himisha, Demichelis Francesca, Kemp Christopher J, Grandori Carla, Cantley Lewis C, Rubin Mark A
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Cancer Discov. 2017 May;7(5):462-477. doi: 10.1158/2159-8290.CD-16-1154. Epub 2017 Mar 22.
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 that integrates whole-exome sequencing 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 Institutional Review Board-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 to discover effective treatment 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 3-D 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. Integration of genomic data with drug screening from personalized and cancer models guides precision cancer care and fuels next-generation research. .
精准医学是一种考虑个体基因、环境和生活方式暴露的影响来定制干预措施的方法。在此,我们描述了一个强大的精准癌症护理平台的开发,该平台将全外显子测序与一个生物样本库相结合,能够对患者来源的肿瘤类器官进行高通量药物筛选。迄今为止,已从一项经机构审查委员会批准的临床试验中招募的769名患者中建立了56种肿瘤来源的类器官培养物和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选择,我们使用高通量药物筛选来发现有效的治疗策略。对来自4例患者(2例子宫恶性肿瘤和2例结肠癌)的肿瘤来源细胞进行分析,确定了有效的药物和药物组合,随后使用三维培养和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型治疗方法的发现,并为标准临床选择已用尽的个体患者提供个性化治疗选择。将基因组数据与来自个性化癌症模型的药物筛选相结合,指导精准癌症护理并推动下一代研究。