# Dual Inhibition of Mitochondrial Matrix Chaperones and Anti-Apoptotic Bcl-2 Family Members for Glioblastoma Therapy.

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $350,000

## Abstract

Project Summary:
Glioblastoma multiforme is the most common primary brain tumor with about 8500 cases
diagnosed each year in the United States. Within a time frame of 15 month virtually all
patients succumb to this detrimental disease despite treatment efforts. Therefore, novel,
ideally tumor specific approaches are necessary to combat these tumors. While single
reagents may efficiently target other tumors, such as hematological malignancies,
Glioblastoma is strikingly different since it is a tumor that is characterized by extensive
heterogeneity, demanding the simultaneous inhibition of ideally several deregulated
pathways. Our previous research has shown that targeting mitochondrial matrix
chaperones displays significant anti-glioma effects. In this proposal, an accomplished
team of investigators will be characterizing a novel treatment concept for glioblastoma by
dual targeting of two deregulated pathways in tumor mitochondria. In the first specific
aim we will test this novel treatment concept, utilizing several in vitro model systems of
glioblastoma with a special focus on so called stem cell-like glioma cells, a population of
tumor cells that drive therapeutic resistance in these neoplasms. Our preliminary data
indicate that our treatment concept efficiently targets this pivotal cell population. In order
to further improve our treatment concept we will study the cell death mechanisms
involved in the combination treatment. In the second aim, we will characterize the
mechanisms that are involved in this treatment approach, which is a centerpiece of our
proposal and may further allow us to better understand and tailor treatments and
potentially to stratify patients that in particular may benefit from this treatment approach.
In the third specific aim we will test this treatment concept in current in vivo model
systems of glioblastoma, which will extend our preliminary data that suggest that this
treatment concept is active in vivo. Overall, this research may enhance our
understanding about the treatment of brain tumors and may potentially allow us to
formulate a novel treatment strategy for glioblastoma.

## Key facts

- **NIH application ID:** 9987713
- **Project number:** 5R01NS095848-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MARKUS D SIEGELIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,000
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987713

## Citation

> US National Institutes of Health, RePORTER application 9987713, Dual Inhibition of Mitochondrial Matrix Chaperones and Anti-Apoptotic Bcl-2 Family Members for Glioblastoma Therapy. (5R01NS095848-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987713. Licensed CC0.

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