Pancreatic Ductal Adenocarcinoma Translational Resource Center (PATReC)

摘要 与其他癌症死亡率下降相反，胰腺导管腺癌的发病率 (PDAC)正在增加，而治疗方法在很大程度上并未成功改善 患者的存活率。尽管免疫疗法的最新进展显示出对各种实体癌症的疗效， PDAC的类似疗效受到复杂的肿瘤微环境(TME)的限制，TME会产生 免疫抑制环境为肿瘤进展提供了条件。因此，大胆的干预可以克服免疫 迫切需要在PDAC TME中设置屏障，以降低这种顽固性疾病引起的死亡率。 U01“PDAC TME翻译研究联盟”是通过美国国家癌症研究所创建的 Moonshot计划加快PDAC中针对TME的创新疗法的进展步伐， 尤其是那些以免疫为基础的模式。我们的建议是对伴星U24的回应 RFA将为五个受资助的财团地点创建一个资源中心，我们称之为胰腺导管 腺癌翻译资源中心(PATReC)。PATReC将由Ignacio博士共同领导 威斯图巴和阿尼尔班·迈特拉是德克萨斯大学MD安德森癌症中心的两位资深分子病理学家 (UTMDACC)在癌症生物标记物、基于组织的分子图谱方面拥有长期的专业知识，并 尊重一名联合领导(AM)，具有PDAC生物学、疾病模型和实验方面的专门知识 治疗学。他们将得到特别的配角支持，包括杰克·李博士(生物统计学)， 安迪·福特雷尔(癌症基因组学和计算生物学)、杰森·罗齐克(生物信息学)和斯坦·汉密尔顿 (NCI Match生物库的联合负责人)。总体目标是在多个方面支持财团的努力 领域包括：为U01之间的协调互动提供行政基础设施 获奖者；促进集中式生物样品银行和分发；支持集中式数据存储 能力；以及有证书的生物统计和生物信息学支持，最终目标是设计 PDAC中针对TME的翻译相关组合干预。在目标1中，我们将支持 U01站点之间的行政协调，确保有效的沟通、合作和 访问快速数据交换，这将促进各个联合体站点的目标。PATReC将 作为整个联盟内虚拟和面对面交流的中心“枢纽”。在目标2中，我们 将利用我们独特的机构基础设施提供集中化的数据管理服务 所有联合体站点都可以通过安全网站轻松访问，并提供生物信息学和生物静力学 为分析和解释数据提供服务。在目标3中，我们将标准化生物银行活动和 制定生物杀虫剂收集、加工和分发的标准操作程序(SOP) AS提供对生物相关的PDAC临床前资源的访问。我们设想PATReC将是 随着我们在针对这一致命疾病的TME方面取得有意义的进展，这是一个不可或缺的因素。

ABSTRACT In contrast to the decline in mortality in other cancers, the incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing, and therapeutic approaches, for the most part, have not been successful at improving survival in patients. Although recent advances in immunotherapy have shown efficacy in various solid cancers, comparable efficacy in PDAC has been limited by a complex tumor microenvironment (TME) that creates an immune suppressive milieu ripe for tumor progression. Thus, bold interventions that can overcome immune barriers in the PDAC TME are urgently needed to reduce the mortality stemming from this recalcitrant disease. The U01 “Consortium for PDAC Translational Studies on the TME” was created through the National Cancer Moonshot initiative to accelerate the pace of progress in innovative therapies targeting the TME in PDAC, especially those geared towards immune-based modalities. Our proposal is in response to the companion U24 RFA to create a resource center for the five funded Consortium sites, which we call Pancreatic Ductal Adenocarcinoma Translational Resource Center (PATReC). The PATReC will be co-led by Drs. Ignacio Wistuba and Anirban Maitra, two established molecular pathologists at UT MD Anderson Cancer Center (UTMDACC) with long-standing expertise in cancer biomarkers, tissue based molecular profiling, and with respect to one co-leader (AM), specific expertise in PDAC biology, disease models and experimental therapeutics. They will be supported by an exceptional supporting cast, including Drs. Jack Lee (biostatistics), Andy Futreal (cancer genomics and computational biology), Jason Roszik (bioinformatics) and Stan Hamilton (co-leader of the NCI MATCH biorepository). The overall goal is to support the consortium efforts in multiple areas including: providing an administrative infrastructure for coordinated interactions amongst the U01 awardees; facilitating centralized biospecimen banking and distribution; enabling centralized data storage capabilities; and credentialed biostatistics and bioinformatics support with the ultimate goal of designing translationally relevant combination interventions targeting the TME in PDAC. In Aim 1, we will support administrative coordination amongst the U01 sites by ensuring effective communication, cooperation, and access to rapid data exchange that will advance the goals of the individual Consortium sites. The PATReC will serve as the central “hub” for virtual and in-person communication across the entire Consortium. In Aim 2, we will utilize our unique institutional infrastructure to provide centralized data management services that will be readily accessible to all Consortium sites via a secure website, and provide bioinformatics and biostatics services for the analyses and interpretation of data. In Aim 3, we will standardize bio-banking activities and develop standard operation procedures (SOPs) for biospecimen collection, processing and distribution, as well as provide access to biologically relevant PDAC preclinical resources. We envision that the PATReC will be an indispensable element as we make meaningful progress towards targeting the TME in this lethal disease.