Integrated Translational Cancer Science Center

描述(由申请人提供)：由SWOG、冷泉港实验室(CSHL)和杰克逊实验室(JAX)组成的综合转化科学中心(ITSC)为应用于癌症医学提供了强大的临床和基础研究专业知识组合。CSHL和JAX都是NCI指定的癌症中心，代表着在癌症基因发现、癌症功能基因组学、创新的肿瘤建模和询问疾病的新技术开发方面的重要集体经验。SWOG是一家首屈一指的临床试验组织，在过去的几十年里建立了多种癌症类型的护理标准。这一联盟将通过阐明可在实验室解决的肿瘤学关键临床问题和挑战，发现可整合到临床试验中的新诊断和治疗方法，并提供在实验室重新解释临床试验结果的渠道，来弥合实验室和临床之间的差距。这种关系将使人们更清楚地了解癌症的潜在机制，并推进旨在开发有效靶向治疗的转化性研究。CSHL和JAX都利用他们对人类癌症分子变化的广泛知识，产生了一系列不同的人类癌症的转基因或原代人类来源(PDX)异种移植小鼠模型，这些模型将被共同用于识别新的治疗脆弱性， 确定原发或继发耐药的机制，并开发新的诊断策略。这些信息将被用来产生关于潜在预测生物标志物的新假设，这些假设可以在SWOG正在进行的随机临床试验中进行研究。新技术的具体例子包括单细胞测序、循环DNA分析、动物模型中的联合临床试验、从基因组数据计算耐药性预测，以及在计算机和动物模型中治疗组合以优化初始效力和避免耐药性。因此，CSHL和JAX的科学努力将为正在进行的临床试验提供信息，并建立促进翻译癌症研究的机制。

DESCRIPTION (provided by applicant): The Integrated Translational Science Center (ITSC) formed between SWOG, Cold Spring Harbor Laboratory (CSHL), and The Jackson Laboratory (JAX) provides a powerful combination of clinical and basic research expertise for application to cancer medicine. CSHL and JAX are both NCI-designated Cancer Centers and represent a significant collective experience in cancer gene discovery, the functional genomics of cancer, innovative tumor modeling, and the development of novel technologies to interrogate the disease. SWOG is a premier clinical trials organization that has established the standard of care for multiple cancer types over the past several decades. This alliance will bridge the gap between the laboratory and the clinic by elucidating the key clinical problems and challenges in oncology that can be addressed in the laboratory, discovering new diagnostic and therapeutic approaches that can be integrated into clinical trials, and providing a conduit for clinical trial results to be re-interpreted in the laboratory. This relationship will lead to a clearer understanding of the mechanisms underlying cancer and advance translational research aimed at developing effective targeted therapies. Both CSHL and JAX have used their extensive knowledge of the molecular alterations in human cancer to generate a diverse array of genetically modified or primary human- derived (PDX) xenograft mouse models of human cancer, and these models will be collectively utilized to identify new therapeutic vulnerabilities, determine mechanisms of primary or secondary drug resistance, and develop novel diagnostic strategies. Such information will be used to generate new hypotheses in regard to potential predictive biomarkers that can be studied in randomized clinical trials being conducted by SWOG. Specific examples of novel expertise include single cell sequencing, circulating DNA analysis, co-clinical trials in animal models, computational prediction of resistance from genomic data, and in silico and animal modeling of therapeutic combinations to optimize initial potency and avoid resistance. The scientific endeavors of CSHL and JAX will therefore inform ongoing clinical trials and establish a mechanism for fostering translational cancer research.