Investigation of a Novel Cancer Stem Cell Population in Ependymoma.

室管膜瘤中新型癌症干细胞群的研究。

基本信息

批准号：
10380564
负责人：
NICHOLAS K FOREMAN
金额：
$ 34.86万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10380564
关键词：
3-Dimensional Activities of Daily Living Address Adult Automobile Driving Biological Biology Brain Neoplasms Cancer Etiology Cell Line Cells Cessation of life Child Childhood Brain Neoplasm Childhood Ependymoma Classification Clinical Data Diagnosis Disease Ependymoma Excision Expression Profiling Flow Cytometry Gene Expression Profiling Grant Heterogeneity Histologic Histology In Vitro Investigation Knowledge Malignant Neoplasms Malignant neoplasm of brain Measures Modeling Modernization Molecular Molecular Profiling Neurosphere Operative Surgical Procedures Outcome Patients Phenotype Population Posterior Fossa Primary Neoplasm Property Radiation Recurrence Relapse Repeat Surgery Research Research Proposals Resected Resolution Sampling Techniques Technology Testing Time Transcript Tumor Biology Tumor Stem Cells base cancer stem cell chemotherapy childhood cancer mortality cohort deep sequencing design exhaustion improved improved outcome in vivo insight medulloblastoma methylomics molecular phenotype mortality mouse model neoplastic cell novel novel therapeutic intervention protein expression refractory cancer relapse risk self-renewal single-cell RNA sequencing stem stem cell population stem cells therapeutic target transcriptome transcriptomics tumor

项目摘要

PROJECT SUMMARY Brain tumors have become the leading cause of cancer-related death in children. Ependymoma (EPN) accounts for a substantial number of these deaths, and unlike in medulloblastoma, no effective chemotherapy has been identified. Most pediatric ependymomas, unlike in adults, occur in the posterior fossa. While aggressive surgery and radiation improve the initial results but even in completely resected and radiated posterior fossa ependymoma the 10-year progression survival is very poor with only approximately one third of these children being without relapse. All relapsed children with ependymoma will relapse again and all will die, often after multiple relapses with damaging repeated surgeries and radiation. There is a desperate need to understand the biology of these tumors better to understand the high, and often delayed, relapses. Bulk examination of childhood ependymoma samples has allowed classification within ependymoma which has had identified subpopulations with early relapse risk but has had no impact on therapy or long-term outcomes. Given that relapses are late, seen most frequently in children who have had complete surgeries and are radiated, we hypothesized that relapses occur from a relatively small number of resistant cancer stem cells present at diagnosis. Preliminary data using single cell RNA seq on posterior fossa ependymoma strengthens this hypothesis and identifies a putative cancer stem cell subpopulation amongst 4 distinct subpopulations. This grant rigorously explores whether we have indeed identified a cancer stem population in childhood ependymoma. Our research intends to fully characterizes the distinct ependymoma subpopulations identified in single cell RNA seq. Potentially targeting a stem cell population at diagnosis in addition to surgery and radiation may improved outcomes for a pediatric brain tumor that has substantial mortality.

项目概要脑肿瘤已成为儿童癌症相关死亡的主要原因。室管膜瘤 (EPN) 此类死亡占很大一部分，与髓母细胞瘤不同的是，没有有效的化疗已被识别。与成人不同，大多数儿童室管膜瘤发生在后颅窝。尽管积极的手术和放疗可以改善最初的结果，但即使是完全切除和放疗后颅窝室管膜瘤 10 年进展生存率非常低，只有大约三分之一这些孩子没有复发。所有室管膜瘤复发的孩子都会再次复发，然后全部死亡，通常是在多次复发且具有破坏性的重复手术和放射治疗之后。迫切需要更好地了解这些肿瘤的生物学特性，以了解高复发率且往往是延迟复发的情况。大部分对儿童室管膜瘤样本的检查允许对室管膜瘤进行分类确定了具有早期复发风险的亚群，但对治疗或长期结果没有影响。鉴于复发较晚，最常见于已接受完整手术且病情稳定的儿童。辐射后，我们假设复发是由相对少数的耐药癌症干细胞引起的诊断时出现。使用单细胞 RNA seq 关于后颅窝室管膜瘤的初步数据得到加强这一假设并在 4 个不同的亚群中确定了一个假定的癌症干细胞亚群。这笔赠款严格探索我们是否确实在儿童时期发现了癌症干细胞群体室管膜瘤。我们的研究旨在全面描述已确定的不同室管膜瘤亚群的特征在单细胞 RNA 测序中除了手术之外，在诊断时还可能针对干细胞群放射治疗可以改善死亡率很高的儿童脑肿瘤的治疗结果。