# SPORE in Brain Cancer

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $2,051,421

## Abstract

SUMMARY: OVERALL
The overarching goal of this Brain Cancer SPORE renewal application is to improve the notoriously poor outcome
of patients with glioblastoma (GBM). This goal will be achieved through the development of a multidisciplinary
and highly translational research program that seeks to discover and rapidly translate novel and mechanistically
diverse treatment strategies, including biological, immunological and targeted strategies, and by developing
prognostic and predictive biomarkers that inform individualized approaches to GBM treatment, while also
exploring pathogenesis and risk through genetic-based epidemiological studies in minority populations. By
pursuing the strategies of this research program, all projects in the current funding period (2013-18) have
successfully transitioned from the bench to clinical trials, including testing of a novel oncolytic virus, Delta-24-
RGD, in multiple clinical trials; completing a biological-endpoint Phase II clinical trial of a PI3K-targeted agent,
BKM-120; meeting IND requirements for a first-in-human trial of a new immune-modulatory p-STAT-3 inhibitor,
WP1066; and validating prognostic biomarkers in clinical trial datasets, while also testing a molecular predictor
of radiation sensitivity. In this renewal application we propose three translational research projects that
organically evolved from the successes of our current SPORE, and which are supported by four mission-critical
Cores (Administrative, Pathology/Biorepository, Biostatistics/ Bioinformatics, Animal). Our Developmental
Research Program (DRP) and Career Enhancement Program (CEP) continue as incubators of new projects and
portals for new investigators. The aims of our projects are:
Project 1: Exploit the capacity of Delta-24-RGD to activate anti-glioma immunity by completing a clinical trial
combining Delta-24-RGD with Pembrolizumab, and by testing next-generation Delta-24-RGD viruses that are
armed with immune stimulatory molecules: OX40L, GITRL, and 4-1BBL, while analyzing anti-Ad5 antibodies as
a biomarker in response to therapy.
Project 2: Attack metabolic vulnerabilities of GBMs through the development and clinical testing of a novel
inhibitor of oxidative phosphorylation (OxPhos), IACS-010759, that efficiently kills GBMs harboring genetic or
epigenetic mutations that impair glycolysis (e.g. ENO1 deletions), and by evaluating a new hypoxia-responsive
PET probe, 18F-FAZA, as a readout of OxPhos inhibition and target engagement of IACS-010759.
Project 3: Decipher germline and somatic genomic landscape of gliomas in Black and Hispanic minority
populations, whose prognosis and survival differ than GBM patients of White European descent. Germline SNP
data will be combined with extensive molecular profiling in case-matched tumors. A detailed analysis will be
performed to determine ancestry composition and how it influences risk for gliomas and clinical outcome in
minorities.

## Key facts

- **NIH application ID:** 10246327
- **Project number:** 5P50CA127001-13
- **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:** 2021
- **Award amount:** $2,051,421
- **Award type:** 5
- **Project period:** 2008-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246327

## Citation

> US National Institutes of Health, RePORTER application 10246327, SPORE in Brain Cancer (5P50CA127001-13). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246327. Licensed CC0.

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