课题基金 / 基金详情

CCSG supplement: HOPE/CARE

CCSG supplement: HOPE/CARE
CCSG 补充:希望/关怀
批准号:
10467882
负责人:
PETER W PISTERS
金额:
$10.0万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-09-01 至 2022-08-31

项目摘要

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中文摘要
翻译
胶质母细胞瘤护理项目:“耐药和进化的细胞分析”。第三年的建议书 分机。 儿童、青少年和青壮年(Aya)和成人的高级别胶质瘤(HGG/GBM) 群体代表一个共同的未得到满足的治疗需求,其基础是细胞的异质性 这些肿瘤及其对治疗的抗药性和残留病,是导致死亡的最终原因。 尽管这一年龄段进行了大量的分子研究,但高级别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,但复发的特征仍然很差。这个项目 利用多机构样本队列解决配对纵向可获得性有限问题 患者样本并将这些队列与最先进的单细胞平台相结合,以分析成人和 儿童脑胶质瘤复发。这一努力是同类研究计划中的第一次。 在整个儿科、阿雅、成人HGG/GBM环境中实施希望工程(儿科和阿雅高级 神经胶质瘤OMICS项目)代表儿科/AYA努力,以及项目CARE(细胞分析 抵抗和进化)代表了成人的努力。我们的中心假设是 在遗传、TME相互作用和表观遗传多样性之间驱动细胞可塑性和燃料 胶质瘤对治疗的适应性和肿瘤内表型的异质性。为了解决这个问题,我们将 处理IDH-野生型GBM和IDH-Wild型GBM之间的遗传、表观遗传和表型异质性的整合 IDH突变型胶质瘤临床样本,有以下三个独立但相互关联的目的:检查 表观遗传改变,如DNA甲基化异常,在驱动GBM的细胞程序中的作用 抵抗治疗(目标1);将体细胞突变的影响定义为GBM细胞状态的函数 以及它们在驱动耐药性方面的作用(目标2);将我们的队列扩大到更多的疾病类别,即 询问原发和复发的idh突变型胶质瘤(目标3)。
英文摘要
Project Glioblastoma CARE: “Cellular Analysis of Resistance and Evolution”. Proposal for Year 3 extension. 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 IDH-wildtype GBM and IDH-mutant gliomas clinical samples, with the following three independent yet interrelated aims: examine the role of epigenetic alterations, such as aberrant DNA methylation, in cellular programs driving GBM resistance to therapy (Aim 1); define the impact of somatic mutations as a function of GBM cellular states and their role in driving resistance (Aim 2); expand our cohort to additional classes of disease, namely interrogate primary and recurrent IDH-mutant gliomas (Aim 3).
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CCSG supplement: Creating an efficient clinical trial build system via the Clinical Trials Rapid Activation Consortium (CTRAC)
Cancer Center Support (CORE) Grant
CCSG supplement Year 2: Creating an efficient clinical trial build system via the Clinical Trials Rapid Activation Consortium (CTRAC)
Cancer Center Support Grant
海外基金