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。

• 批准号: 10577748
• 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
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10577748
• 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; Maps; Measures; Modeling; Modernization; Molecular; Molecular Profiling; Neurosphere; Operative Surgical Procedures; Outcome; Patients; Phenotype; Population; Posterior Fossa; Primary Neoplasm; Property; Radiation; Recurrence; Recurrent tumor; Relapse; Repeat Surgery; Research; Research Proposals; Resected; Resolution; Sampling; Techniques; Technology; Testing; Time; Transcript; Tumor Biology; Tumor Stem Cells; cancer stem cell; chemotherapy; childhood cancer mortality; cohort; deep sequencing; design; 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; transcriptome sequencing; transcriptomics; tumor; tumor initiation

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.

项目摘要 脑肿瘤已成为儿童癌症相关死亡的主要原因。室管膜瘤（EPN） 在这些死亡中占相当大的比例，与髓母细胞瘤不同， 已经被确认了与成人不同，大多数小儿室管膜瘤发生在后颅窝。而 积极的手术和放射治疗改善了最初的结果，但即使在完全切除和放射治疗， 后颅窝室管膜瘤的10年进展生存率非常低，只有大约三分之一的患者， 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，所有人都会死亡， 通常是在多次复发后，伴随着破坏性的反复手术和放射治疗。我们迫切需要 更好地了解这些肿瘤的生物学，以了解高，往往是延迟，复发。散装 儿童室管膜瘤样本的检查允许室管膜瘤的分类， 确定了具有早期复发风险的亚群，但对治疗或长期结局没有影响。 考虑到复发是晚期的，最常见于已经完成手术的儿童， 我们假设复发发生在相对少量的耐药癌症干细胞上， 诊断时在场。使用单细胞RNA测序对后颅窝室管膜瘤进行强化的初步数据 这一假设并在4个不同的亚群中鉴定出推定的癌症干细胞亚群。 这项资助严格探索了我们是否确实在儿童时期发现了癌症干细胞人群 室管膜瘤我们的研究旨在充分描述不同的室管膜瘤亚群， 在单细胞RNA测序中，除了手术外，还可能在诊断时靶向干细胞群体， 放射治疗可以改善死亡率很高的小儿脑肿瘤的预后。