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 前列腺癌进展为转移性去势抵抗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 推动肿瘤进展的细胞状态和细胞类型，而且更多的研究表明， 肿瘤微环境的作用。因此，我们提出了一个新的计划项目来调查 肿瘤细胞与周围间质及免疫微环境相互作用促进前列腺生长 癌症进展、转移和治疗耐药。我们的建议是高度整合的，因为它将 一个由四名杰出调查人员(Michael Shenin，Charles Sawyers，Cory Abate-shen， Massimo Loda)在前列腺癌研究中拥有互补的专业知识以及实质性的跟踪 协作交互的记录。 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Cory Abate-shen(哥伦比亚 欧文大学医学中心将研究前列腺癌的细胞内部和外部驱动因素 骨转移。项目3，由兼任总体PI的Michael Shenin(CUIMC)领导，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 马西莫·罗达(Weill Cornell Medicine)将为所有三个项目提供多种基于病理学的服务。 最后，由Michael Shenin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、生物统计支持以及整体方案的协调、资源管理和 由内部和外部咨询委员会进行审查。总而言之，这一高度协同的计划将阐明 内在和外在信号的整合，驱动了去势抵抗、转移倾向和 前列腺癌的神经内分泌分化，并将提供对间质和 改善治疗方法的免疫微环境。