Investigating cell-intrinsic and extrinsic interactions in prostate cancer at the single cell level

项目总结/摘要 前列腺癌进展为转移性去势抵抗性疾病仍然是一个主要的 健康问题。单细胞方法的最新进展揭示了广泛的异质性和复杂性 的细胞状态和细胞类型，推动肿瘤的进展，和其他研究表明，中央 肿瘤微环境的作用。因此，我们提出了一个新的计划项目，以调查 肿瘤细胞及其周围基质和免疫微环境之间相互作用促进前列腺增生 癌症进展、转移和治疗抗性。我们的建议是高度综合的，因为它汇集了 一个由四位杰出的研究人员组成的多机构团队（Michael Shen，Charles Sawyers，Cory Abate-Shen， Massimo Loda）在前列腺癌研究中具有互补的专业知识以及大量的跟踪 协作互动的记录。 我们围绕以下项目和核心构建了我们的应用程序：项目1，由Charles领导 Sawyers（纪念斯隆-凯特琳癌症中心）将研究免疫和基质因素， 促进前列腺癌和去势反应。项目2，由科里Abate-Shen（哥伦比亚 欧文大学医学中心; CUIMC），将研究前列腺癌的细胞内在和外在驱动因素 转移至骨。项目3由Michael Shen（CUIMC）领导，他也是整体PI，将分析内在的 以及促进前列腺神经内分泌分化的外在因素。核心A（病理生物学），由 Massimo Loda（Weill Cornell Medicine）将为所有三个项目提供多种病理学服务。 最后，由Michael Shen领导的核心B（行政和数据管理）将通过以下方式支持每个项目： 数据管理，生物统计支持，整体计划的协调，资源管理， 内部和外部咨询委员会的审查。总之，这个高度协同的计划将阐明 整合内在和外在信号，驱动去势抵抗，转移向性， 神经内分泌分化的前列腺癌，并将提供翻译的见解，基质和 免疫微环境，以改善治疗方法。

Project Summary/Abstract Prostate cancer progression to metastatic castration-resistant disease continues to represent a major health issue. Recent advances in single-cell approaches have revealed extensive heterogeneity and complexity of cell states and cell types that drive tumor progression, and additional studies have demonstrated the central role of the tumor microenvironment. Consequently, we are proposing a new Program Project to investigate the interplay between tumor cells and their surrounding stromal and immune microenvironment in promoting prostate cancer progression, metastasis, and treatment-resistance. Our proposal is highly integrated as it brings together a multi-institutional team of four distinguished investigators (Michael Shen, Charles Sawyers, Cory Abate-Shen, Massimo Loda) in the study of prostate cancer who have complementary expertise as well as a substantial track record of collaborative interactions. We have structured our application around the following projects and cores: Project 1, led by Charles Sawyers (Memorial Sloan-Kettering Cancer Center), will investigate the immune and stromal factors that promote prostate adenocarcinoma and castration-response. Project 2, led by Cory Abate-Shen (Columbia University Irving Medical Center; CUIMC), will investigate the cell intrinsic and extrinsic drivers of prostate cancer metastasis to bone. Project 3, led by Michael Shen (CUIMC), who is also overall PI, will analyze the intrinsic and extrinsic factors that promote prostate neuroendocrine differentiation. Core A (Pathobiology), led by Massimo Loda (Weill Cornell Medicine), will provide multiple pathology-based services to all three Projects. Finally, Core B (Administrative and Data Management), led by Michael Shen, will support each Project through data management, biostatistical support, and coordination of the overall program, resource management, and review by the Internal and External Advisory Boards. Together, this highly synergistic program will elucidate the integration of intrinsic and extrinsic signals that drive castration-resistance, metastatic tropism, and neuroendocrine differentiation in prostate cancer, and will provide translational insights into the stromal and immune microenvironments for improved therapeutic approaches.