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.

项目总结/文摘