Integrated Translational Cancer Science Center

描述（由申请人提供）：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）为癌症医学应用提供了临床和基础研究专业知识的强大组合。CSHL和JAX都是NCI指定的癌症中心，代表了癌症基因发现，癌症功能基因组学，创新肿瘤建模和开发新技术来询问疾病的重要集体经验。SWOG是一家领先的临床试验组织，在过去几十年中为多种癌症类型建立了护理标准。该联盟将通过阐明实验室可以解决的肿瘤学关键临床问题和挑战，发现可以整合到临床试验中的新诊断和治疗方法，并为实验室重新解释临床试验结果提供渠道，从而弥合实验室和临床之间的差距。这种关系将使我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研究。CSHL和JAX都利用他们对人类癌症分子改变的广泛知识来产生人类癌症的多种遗传修饰或原发性人源性（PDX）异种移植小鼠模型，并且这些模型将被共同用于鉴定新的治疗弱点， 确定原发性或继发性耐药的机制，并开发新的诊断策略。这些信息将用于生成关于潜在预测生物标志物的新假设，这些生物标志物可以在SWOG进行的随机临床试验中进行研究。新的专业知识的具体例子包括单细胞测序，循环DNA分析，在动物模型中的共同临床试验，从基因组数据的耐药性的计算预测，以及在计算机和动物模型的治疗组合，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，并建立促进转化癌症研究的机制。

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.