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Molecular Tumorigenesis of Bladder Cancer

膀胱癌的分子肿瘤发生

基本信息

批准号：
10661060
负责人：
XUE-RU WU
金额：
$ 134.44万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-12 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10661060
关键词：
Affect Apoptotic Authorship Awareness BIRC4 gene Basic Science Biological Biological Assay Biological Markers Biology Bladder Cells Clinical Research Collaborations Cultured Cells DNA Damage DNA Repair DNA Repair Inhibition Data Dedications Development Diagnosis Differentiation and Growth Disease Distant Electronic cigarette Ensure Funding Genetic Genetic Drift Genetic Engineering Genetic study Genetically Engineered Mouse Heterogeneity High Prevalence Human Incidence Invaded Investigation Joints Knowledge Link Lung Adenocarcinoma Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of urinary bladder Medical Medical Care Costs Modeling Molecular Moon Mus Muscle Mutation Neoplasm Metastasis Nicotine Nitrosamines Outcome Paper Papillary Pathway interactions Persons Phenotype Play Productivity Proteins Publishing Reagent Recording of previous events Research Personnel Research Project Grants Role Seminal Services Signal Pathway Signal Transduction Survival Rate Testing Tobacco smoke Translational Research United States Urothelial Cell Urothelial Hyperplasia Urothelium Variant Woman Work base bladder cancer prevention cancer cell cancer heterogeneity carcinogenicity chemical carcinogenesis cigarette smoke-induced combinatorial cost cost effectiveness e-cigarette smoke exome exposure to cigarette smoke immune checkpoint blockade in vivo innovation interdisciplinary approach lifetime risk men molecular subtypes mouse genetics muscle invasive bladder cancer novel novel marker novel therapeutic intervention novel therapeutics operation prevent programs repaired stem cells theranostics therapeutically effective transcriptome tumorigenesis vapor whole genome

项目摘要

Overall: Project Summary Of the most prevalent cancers in the United States over the last three decades, bladder cancer (BC) has consistently ranked the fifth in annual incidence and the first in medical expenses on a per-case basis. Despite its high prevalence and staggering medical costs, BC is until recently among the least studied cancers with limited efforts in basic, translational and clinical research. Consequently, few assays and biomarkers exist to reliably diagnose BC and predict its progression and few new therapeutic approaches are available to effectively manage BC. Compounding this is the fact that BC is highly heterogeneous comprised of major phenotypic variants and molecular subtypes, as evidenced by previous genetic studies and recent whole- genome/-exome/transcriptome analyses. Over the last five years, the investigators of our PO1 Team have worked together in a highly synergistic and collaborative manner in tackling the biological bases of BC heterogeneity and made significant strides in: discerning the combinatorial genetic drivers of major BC variants; establishing DNA damage and repair as distinguishing features of different types of BC; establishing XIAP as a critical driver of BC invasion; and identifying urothelial subpopulations as potential progenitor cells of BC variants. This renewal application builds on this forward momentum and focuses on a much deeper and expanded scientific theme – the genetic, carcinogenomic, molecular and cellular underpinnings of BC heterogeneity, by asking several important new questions. What dictates the origin(s) of major BC variants: divergent genetic drivers versus divergent progenitor cells (Project 1; P1)? Do the nitrosamines converted from nicotine in E-cigarette vapor within host cells cause muscle-invasive BC and how do they affect urothelial DNA damage and repair (P2)? And is there a master switch that drives the formation of basal-subtype muscle- invasive BC (P3)? Results from this highly coordinated, collaborative team effort should contribute to the major leap forward in our understanding of the biological bases of BC heterogeneity, leading to the development of novel biomarkers and therapeutics for this highly prevalent but extremely under-studied disease.

总体：项目总结