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

在单细胞水平上研究前列腺癌的细胞内在和外在相互作用

• 批准号: 10612346
• 负责人: MICHAEL M. SHEN
• 金额: $ 205.58万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612346
• 关键词: Abate; Affect; American; Androgen Antagonists; Androgen Receptor; Androgens; Antiandrogen Therapy; Biological Assay; Biometry; Cancer Etiology; Candidate Disease Gene; Castration; Cells; Cessation of life; Data Set; Development; Disease Resistance; Epithelial-Stromal Communication; Genetically Engineered Mouse; Group Meetings; Health; Heterogeneity; Human; Image Analysis; Immune; Infiltration; Institution; International; Intrinsic factor; Investigation; Joints; Malignant Neoplasms; Malignant neoplasm of prostate; Mediating; Medical center; Medicine; Memorial Sloan-Kettering Cancer Center; Metastatic Neoplasm to the Bone; Modeling; Molecular; Mus; Myelogenous; Neoplasm Metastasis; Neuroendocrine Prostate Cancer; Neurosecretory Systems; New York City; Office of Administrative Management; Organogenesis; Organoids; Pathologic; Pathology; Pathway interactions; Population; Prostate; Prostate Adenocarcinoma; Prostate Cancer therapy; Prostatic Neoplasms; Publications; Regulation; Research Personnel; Resistance; Resources; Retrieval; Role; Running; Sampling; Services; Signal Transduction; Specific qualifier value; Structure; System; Systems Analysis; Therapeutic; Tissue Microarray; Tissue Sample; Tropism; Universities; bone; cell type; cellular imaging; cofactor; data management; deprivation; human tissue; improved; insight; lens; member; men; molecular pathology; multidisciplinary; multiparametric imaging; neoplastic cell; neuroendocrine differentiation; new technology; novel strategies; programs; prostate cancer metastasis; prostate cancer progression; response; single cell analysis; single cell sequencing; single-cell RNA sequencing; technology development; therapy resistant; tumor; tumor microenvironment; tumor progression; tumor-immune system interactions

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.

项目摘要/摘要 前列腺癌向转移性cast割疾病的发展继续代表主要 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 驱动肿瘤进展的细胞态和细胞类型的其他研究表明了中心 肿瘤微环境的作用。因此，我们正在提出一个新的计划项目，以调查 肿瘤细胞及其周围的基质和免疫微环境之间的相互作用在促进前列腺中 癌症的进展，转移和耐药性。我们的建议高度融合在一起 一支由四名杰出调查人员组成的多机构团队（迈克尔·沉（Michael Shen），查尔斯·索耶（Charles Sawyers），科里·阿巴特·舒（Cory Abate-Shen）， Massimo Loda）在具有互补专业知识的前列腺癌研究中 协作互动的记录。 我们已经围绕以下项目和核心构建了我们的应用程序：由查尔斯领导的项目1 锯豆（纪念斯隆 - 凯特林癌症中心）将调查免疫和基质因素 促进前列腺腺癌和去势反应。项目2，由Cory Abate-Shen领导（哥伦比亚 大学欧文医学中心； CUIMC），将研究细胞的固有和外在驱动因素 转移到骨头。由PI总体PI的Michael Shen（Cuimc）领导的项目3将分析固有的 以及促进前列腺神经内分泌分化的外部因素。核心A（病理学），由 Massimo Loda（Weill Cornell Medicine）将为所有三个项目提供多种基于病理的服务。 最后，由Michael Shen领导的Core B（行政和数据管理）将通过 数据管理，生物统计学支持以及整体计划，资源管理和 由内部和外部咨询委员会进行审查。这项高度协同的程序将阐明 促进castration抗性，转移性的托和外在信号的整合 前列腺癌中神经内分泌分化，并将提供转化的见解 免疫微环境改进了治疗方法。