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).

项目摘要 小儿，青少年和年轻人（aya）和成人的高级神经瘤（HGG/GBM） 种群代表了由细胞异质性的基础的常见未满足的治疗需求 这些肿瘤及其对治疗性耐药性和残留疾病的贡献，是死亡的最终原因。 尽管在该年龄范围内进行了大量分子研究，但高级胶质瘤和胶质母细胞瘤在 尽管是大多数临床试验的背景，但复发性的特征仍然很差。这个项目 利用多机构标本队列，以解决配对纵向有限的可用性 患者标本，并将此类同类与最先进的单细胞平台相结合，以介绍成人和 小儿神经胶质瘤通过复发。这项工作代表了研究计划的第一个连续性 遍布小儿，AYA，成人HGG/GBM景观，带有希望（小儿和Aya高级 Glioma OMICS项目）代表儿科/AYA努力和项目护理（细胞分析 抵抗和进化）代表成人努力。我们的中心假设是 遗传，TME相互作用和表观遗传多样性驱动细胞可塑性，并为胶质瘤适应至 治疗和肿瘤内表型异质性。为了解决这个问题，我们将解决 HGG样品的遗传，表观遗传和表型异质性，以下两个 独立但相互关联的目的：小儿和AYA中癌细胞的单细胞多摩变测序 高级神经胶质瘤（AIM 1）；小儿非免疫微环境的单核测序 和AYA高级神经胶质瘤（AIM 2）。