# Differential response of glioblastomas to microtubule targeting agents

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $353,812

## Abstract

Microtubule targeting agents (MTAs) are commonly prescribed to treat many types of cancers; yet their use for
the treatment of glioblastomas (GBM) is limited by their poor brain penetrance. We developed a new series of
MTAs (ST-compounds) that destabilize microtubules (MT) and kill GBM through a novel mechanism of action
(MOA). Our recent results show that ST-compounds pass the blood brain barrier (BBB) and exhibits in vivo
therapeutic efficacy in a preclinical mouse model of GBM.
 This new R01 uses complementary expertise and approaches to study how the novel MOA of ST-
compounds differs from known MTAs and its therapeutic efficacy in several preclinical mouse model of GBM.
Specifically, it leverages several innovative technologies, including live-cell imaging and artificial learning
algorithms, to better understand why GBM are particularly sensitive to the antitumor activity of ST-compounds.
Experiments will be performed on patient-derived GBM (PD-GBM) in culture and include measure of real-time
changes in GBM cell migration, cell division and cell cycle fate as fundamental readouts of tumorigenesis. In
vivo experiments will be done on both genetic orthotopic mouse models of GBM and orthotopic mouse model
of PD-GBM. Our aims are:
1: Differential impact of MTAs on the migration and mitosis of GBM in culture.
2: Differential impact of MTAs on the viability and fate of GBM in culture.
3: Therapeutic efficacy and mechanism of ST-401 in GBM models in vivo.
Our immediate goal is to increase our understanding of the precise MOA by which MTAs regulate GBM
tumorigenesis and how this interacts with standard care treatments. This work will help set a solid foundation
for the development of a new class of MTAs for the safe treatment of patients diagnosed with GBM.

## Key facts

- **NIH application ID:** 10434745
- **Project number:** 5R01CA244213-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Nephi Stella
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $353,812
- **Award type:** 5
- **Project period:** 2020-07-02 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434745

## Citation

> US National Institutes of Health, RePORTER application 10434745, Differential response of glioblastomas to microtubule targeting agents (5R01CA244213-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10434745. Licensed CC0.

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