# NAD+ Pathway Signaling in Glioblastoma Tumor Growth and Therapy Resistance

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $381,536

## Abstract

ABSTRACT
Glioblastoma, the most common primary malignant brain tumor in adults, remains incurable despite multimodal
therapy, necessitating the discovery of new therapeutic strategies. Emerging evidence indicates that the
unique metabolic profile of cancer cells interfaces with signal transduction and transcriptional programs to
stimulate malignant behavior. Nicotinamide adenine dinucleotide (NAD+) plays a pivotal role in cancer cell
metabolism, but how NAD+ and its regulation impacts functionally relevant signaling events in glioblastoma has
not been well understood. We recently found that high expression of NAMPT, the rate-limiting step in NAD+
biosynthesis, in glioblastoma tumors is associated with poor overall survival in patients and demonstrated that
NAMPT is essential for self-renewal and in vivo tumor growth in primary glioblastoma cells, indicating a
requirement for NAD+ to maintain malignant behavior. We also identified a NAD+-dependent transcriptional
program mediated by transcription factor E2F2, which is required for the self-renewal and clonogenic survival
of glioblastoma cells. In this project, we will first elucidate the molecular mechanisms that link NAD+ to the
E2F2-dependent transcriptional program in glioblastoma. We will then examine the role of NAD+ generation in
glioblastoma cells focusing on NAMPT regulation, with examination of metabolic correlates using human tumor
samples. Finally, we will investigate the ability of NAMPT inhibition in vivo to enhance the therapeutic efficacy
of radiation therapy, a major arm of the current standard-of-care, and further delineate the mechanism by
which NAMPT dictates radiation responsiveness. The immediate goal of this project is to identify the
mechanisms of NAD+-dependent metabolic reprogramming in glioblastoma, with the long-term goal of
developing novel NAD+ pathway-directed strategies to disrupt glioblastoma growth and increase the
effectiveness of current therapies.

## Key facts

- **NIH application ID:** 9934310
- **Project number:** 5R01NS106612-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Albert Hong-Jae Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,536
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934310

## Citation

> US National Institutes of Health, RePORTER application 9934310, NAD+ Pathway Signaling in Glioblastoma Tumor Growth and Therapy Resistance (5R01NS106612-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934310. Licensed CC0.

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