# SPORE in Brain Cancer

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $2,088,365

## Abstract

SUMMARY: OVERALL
The overarching goal of this Brain Cancer SPORE renewal application is to reverse the notoriously poor outcome
of patients with glioblastoma (GBM) and medulloblastoma (MB), the most common primary tumors in adults and
children, respectively. This goal is achieved through a focused pursuit of our central hypothesis that an
organized, multidisciplinary, integrated, flexible, and highly translational (“bench-to-bedside-and-back”) research
program will lead to advances in the treatment of brain cancers. We seek to discover mechanistically diverse
therapeutic strategies (including bio-therapies, targeted therapies, cellular therapies and immunotherapies) that
attack intrinsic vulnerabilities of brain cancers, develop these strategies through rigorous preclinical testing, and
deploy them in novel window-of-opportunity clinical trials. By pursuing this hypothesis over the past three funding
cycles, we have successfully transitioned multiple agents from the bench to bedside by successfully undertaking
a remarkable twelve clinical trials, including trials of Delta-24-RGD, an oncolytic virus , which we tested alone
or in combination with the checkpoint inhibitor (ICI) pembrolizumab; Delta-24-RGDOX, an immune activating
oncolytic viruses; bone marrow mesenchymal stem cells loaded with Delta-24; targeted therapies including
BKM120, a PI3Kinase inhibitor; WP1066, a pSTAT3 inhibitor; IACS-010759, an OxPhos inhibitor; and
engineered cord blood-derived Natural Killer (NK) cells. Also, in our current funding cycle we deciphered the
genomic landscape of gliomas in underrepresented minority Black and Hispanic populations. Building on this
exceptional track record, in this renewal we propose three fully translational projects that are specifically focused
on overcoming the notoriously immunosuppressive tumor microenvironment (TME) of GBMs and MBs, and
which are supported by four mission-critical Cores (Administrative, Pathology/Biorepository, Biostatistics/
Bioinformatics, Animal). Our Developmental Research and Career Enhancement Programs continue as
incubators of new projects and portals for new investigators, with two of our proposed projects coming directly
from these programs. The aims of our projects are: Combine Delta-24-RGD with genetically engineered NK cells,
testing the hypothesis that oncolytic viruses and NK cells can shape the GBM immune TME to synergistic
therapeutic effect (Aim 1): Restore phagocytosis in GBM-associated myeloid (GAMs) cells by targeting the
QKI/PPARβ/RXRα (QPR) complex, testing the hypothesize that QPR agonists (bexarotene/ KD3010) can drive
GAMs from an immunosuppressive to an anti-glioma state through QPR’s role in phagocytosis and antigen
presentation (Aim 2); And exploit the immune consequences of U1 mutations in Sonic Hedgehog (Shh) MB,
testing the hypothesis that the post transcriptional hyper-mutated state caused by a point mutation (r.3A>G) in
the non-coding small nuclear RNA U1 of Shh MBs will exquisitely se...

## Key facts

- **NIH application ID:** 10847565
- **Project number:** 2P50CA127001-16
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Juan Fueyo
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,088,365
- **Award type:** 2
- **Project period:** 2008-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847565

## Citation

> US National Institutes of Health, RePORTER application 10847565, SPORE in Brain Cancer (2P50CA127001-16). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10847565. Licensed CC0.

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