# Project Glioblastoma CARE: "Cellular Analysis of Resistance and Evolution". Proposal for Year 3 extension.

> **NIH NIH P30** · DUKE UNIVERSITY · 2021 · $100,000

## Abstract

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).

## Key facts

- **NIH application ID:** 10466601
- **Project number:** 3P30CA014236-47S2
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Michael B Kastan
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $100,000
- **Award type:** 3
- **Project period:** 1997-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466601

## Citation

> US National Institutes of Health, RePORTER application 10466601, Project Glioblastoma CARE: "Cellular Analysis of Resistance and Evolution". Proposal for Year 3 extension. (3P30CA014236-47S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10466601. Licensed CC0.

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