Abramson Cancer Center Support Grant

艾布拉姆森癌症中心支持补助金

• 批准号: 10469216
• 负责人: ROBERT H VONDERHEIDE
• 金额: $ 36.76万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469216
• 关键词: Address; Adolescent and Young Adult; Adult; Adult Glioma; Age; Automobile Driving; Cancer Center Support Grant; Caring; Cause of Death; Cell Nucleus; Cells; Childhood; Childhood Glioma; Clinical; Clinical Trials; Computer Analysis; Epigenetic Process; Evolution; Genetic; Glioblastoma; Glioma; Heterogeneity; Malignant Neoplasms; Malignant neoplasm of brain; Modality; Molecular; Patients; Phenotype; Population; Recurrence; Research; Residual Tumors; Resistance; Sampling; Specimen; Systems Biology; Testing; Therapeutic; cancer cell; cohort; multiple omics; novel therapeutics; programs; therapy resistant; tumor; tumor heterogeneity

PROJECT SUMMARY High grade gliomas (HGG/GBM) across the pediatric, adolescent and young adult (AYA), and adult populations represent a common unmet therapeutic need underpinned by the cellular heterogeneity of these tumors and its contribution to treatment resistance and residual disease, the ultimate cause of death. Despite numerous molecular studies across this age spectrum, high grade glioma and glioblastoma at recurrence remain poorly characterized, despite being the context for most clinical trials. This project leverages multi-institutional specimen cohorts that addresses the limited availability of paired longitudinal patient specimens and combines such cohorts with state-of-the-art single-cell platforms to profile adult and pediatric gliomas through recurrence. This effort represents a first in kind continuum of research initiative across the pediatric, AYA, adult HGG/GBM landscape with Project HOPE (Pediatric and AYA High-Grade Glioma Omics Project) representing the pediatric/AYA effort, and Project CARE (cellular analysis of resistance and evolution) representing the adult effort. Our central hypothesis is that the interplay between genetic, TME interactions and epigenetic diversity drive cellular plasticity and fuels gliomas adaptation to therapy and intra-tumoral phenotypic heterogeneity. To address this, we will tackle the integration of genetic, epigenetic, and phenotypic heterogeneity across HGG samples, with the following two independent yet interrelated aims: Single cell multi-omic sequencing of cancer cells in pediatric and AYA high-grade gliomas (Aim 1); Single nucleus sequencing of the non-immune microenvironment of pediatric and AYA high-grade gliomas (Aim 2).

项目概要 儿童、青少年和青年 (AYA) 以及成人的高级别胶质瘤 (HGG/GBM) 人群代表了一种常见的未满足的治疗需求，其基础是细胞异质性 这些肿瘤及其对治疗耐药性和残留疾病的贡献，这是死亡的最终原因。 尽管针对这个年龄段进行了大量的分子研究，但高级别神经胶质瘤和胶质母细胞瘤 尽管复发是大多数临床试验的背景，但复发的特征仍然不明确。这个项目 利用多机构样本队列来解决配对纵向样本的有限可用性 患者标本并将此类群体与最先进的单细胞平台相结合，以分析成人和 儿童神经胶质瘤复发。这项工作代表了同类研究计划中的第一个连续体 与 Project HOPE（儿科和 AYA 高级 神经胶质瘤组学项目）代表儿科/AYA 的工作，以及 CARE 项目（细胞分析） 抵抗和进化）代表成人的努力。我们的中心假设是，之间的相互作用 遗传、TME 相互作用和表观遗传多样性驱动细胞可塑性并促进神经胶质瘤适应 治疗和肿瘤内表型异质性。为了解决这个问题，我们将解决以下问题： HGG 样本之间的遗传、表观遗传和表型异质性，有以下两个 独立但相互关联的目标：儿科和 AYA 癌细胞的单细胞多组学测序 高级别神经胶质瘤（目标 1）；儿科非免疫微环境的单核测序 和 AYA 高级神经胶质瘤（目标 2）。