# Targeting Amino Acid Metabolism in Glioblastoma

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $574,427

## Abstract

ABSTRACT
Glioblastomas rank among the most lethal of all human cancers. Current therapy includes maximal surgical
resection, followed by combined radiotherapy and oral chemotherapy (temozolomide), and adjuvant
temozolomide. However, current glioblastoma therapy offers only palliation. Median survival for glioblastoma
patients has been reported to be 15-21 months, but these data are derived from patients with favorable age
and performance status. Glioblastoma ranks among the human cancers most thoroughly studied, yet
precision medicine efforts have demonstrated very limited efficacy. Like many cancers, glioblastomas display
altered metabolism that promotes tumor growth, often through the generation of metabolites that promote
epigenetic reprogramming. In the current proposal, we focus on the role of specific essential amino acids that
appear to the preferentially taken up by brain tumor cells. Upon cellular entry, amino acids can undergo
catabolism to generate bioactive intermediates that can alter the chromatin landscape and modulate tumor-
immune interactions.
Based on this background, we investigated differential expression of metabolic pathways and amino acid
levels between glioblastoma cells and neural stem cells, revealing critical selective dependencies in tumor
cells due to both altered gene expression and genetic lesions. As a result, glioblastoma cells suppress the
anti-tumor immune response. In the proposed studies, we will investigate the molecular and cell biology
mechanisms through which selective amino acid metabolism regulates brain tumor growth and immune
interplay. Systems to be used include patient-derived cultures, organoids, and xenografts to determine the
molecular determinants of amino acid catabolism and epigenetic reprogramming. To translate these efforts
into novel preclinical paradigms, we propose to use dietary manipulations that have been developed for
treatment of inborn errors of metabolism, including those that affect the brain. These dietary interventions
can potentially be combined with other therapies, including targeted therapies and immune checkpoint
inhibitors, to target glioblastomas. Collectively, the proposed studies will lay the foundation for improved
understanding of tumor metabolism in brain tumor biology with possible application to oncologic care.

## Key facts

- **NIH application ID:** 10980641
- **Project number:** 1R01NS134724-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kalil G Abdullah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $574,427
- **Award type:** 1
- **Project period:** 2024-09-20 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980641

## Citation

> US National Institutes of Health, RePORTER application 10980641, Targeting Amino Acid Metabolism in Glioblastoma (1R01NS134724-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10980641. Licensed CC0.

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