Core C: Patient Derived Xenograft (PDX)/ Syngeneic Mouse Core

核心C摘要 患者来源的异种移植(PDX)和同基因小鼠黑色素瘤核心服务。 尽管最近针对转移性人类黑色素瘤的靶向治疗和免疫治疗取得了进展， 先天、获得性和获得性耐药性的出现限制了临床生存的益处。这一核心将有助于 本PPG中三个项目的总体目标和具体目标。定义抗性机制 体外系统是重要的第一步，但其概括肿瘤内和肿瘤内的能力有限。 异质性，不能复制免疫和基质环境影响。的发展。 保持患者肿瘤特征的患者衍生异种移植(PDX)模型将确保 本PPG中每个项目中拟议研究的临床和体内相关性。PDX与小鼠黑色素瘤 CORE的目标是进行预期的肿瘤活检收集，以创建一个完整的 特色化的PDX型号。核心将提供对已经开发的PDX模型的生物库的访问 来自Core B和外部合作者提供的活检样本以及小鼠黑色素瘤 代表转移性人类黑色素瘤基因组多样性的模型。它还将生成以下模型 对目前FDA批准或临床测试的靶向治疗和建议的关键组合产生抵抗性 这个PPG。我们还将从PDX模型中生成细胞系，以使项目的调查人员能够执行 一级机理分析。最后，核心将生成一套时间/空间多组数据， 可以由每个项目挖掘，以确定最初用作证据的特定模型 概念，然后组装具有足够多样性的面板，以评估重复性或生物效应 仅限于某些基因组、表观基因组或免疫学背景。

CORE C ABSTRACT Patient-derived Xenograft (PDX) and Syngeneic Mouse Melanoma Core services. Despite recent development of targeted therapies and immunotherapies for metastatic human melanoma, innate, adaptive and acquired resistance arise and limit clinical survival benefits. This core will subserve the overarching goals and specific aims of each of the three Projects in this PPG. Defining resistance mechanisms in an in vitro system is an important first step but is limited in its capacity to recapitulate inter- and intra-tumor heterogeneity and incapable of reproducing immune and stromal environmental impacts. The development of Patient-derived Xenograft (PDX) models that maintain the characteristics of the patient's tumor will ensure clinical and in vivo relevance of proposed studies in each Project in this PPG. The PDX and murine melanoma core aims to perform a prospective collection of tumor biopsies in order to create an extensive library of fully characterized PDX models. The core will provide access to a biobank of PDX models that have been developed from biopsy samples provided by the Core B and from outside collaborators as well as murine melanoma models representing the genomic diversity of metastatic human melanoma. It will also generate models of acquired resistance to currently FDA-approved or clinically-tested targeted therapies and key combinations proposed in this PPG. We will also generate cell lines from PDX models to enable investigators of the Projects to perform first-level mechanistic analyses. Finally, the core will generate a suite of temporal/spatial multi-omic data that can be mined by each of the Projects to identifiy specific models that would be initially used as proof-of- concepts and later to assemble panels with sufficient diversity to evaluate reproducibility or biologic effects restricted to certain genomic, epigenomic or immunologic contexts.