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

核心C摘要 患者源性异种移植（PDX）和同基因小鼠黑色素瘤核心服务。 尽管最近发展了针对转移性人黑色素瘤的靶向疗法和免疫疗法， 先天性、适应性和获得性抗性的出现限制了临床存活益处。这一核心将有助于 本项目规划中三个项目的总体目标和具体目标。确定耐药机制 在体外系统中是重要的第一步，但其再现肿瘤间和肿瘤内的能力有限 异质性和不能复制免疫和基质环境的影响。的发展 保持患者肿瘤特征的患者来源的异种移植物（PDX）模型将确保 本PPG中每个项目中拟定研究的临床和体内相关性。PDX与小鼠黑色素瘤 核心的目的是进行前瞻性收集肿瘤活检，以建立一个广泛的图书馆， 特征PDX模型。该核心将提供对已开发的PDX模型的生物库的访问 来自核心B和外部合作者提供的活检样本以及鼠黑色素瘤 代表转移性人黑色素瘤基因组多样性的模型。它还将生成 对目前FDA批准或临床试验的靶向治疗和 这个PPG。我们还将从PDX模型中产生细胞系，使项目的研究人员能够进行 第一层次机理分析。最后，核心将生成一套时间/空间多组学数据， 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，以评估再现性或生物效应 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.