# Chronotherapy for glioblastoma

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2021 · $236,250

## Abstract

Project Summary
This proposal tests the fundamental hypothesis that circadian rhythms in brain tumors provide a
temporal therapeutic window during which the efficacy of standard treatments may be
substantially optimized. Timed delivery of chemotherapy, or chronotherapy, has an established
role in colorectal cancer and leukemia but has never been evaluated in brain tumors. Here we
build on exciting preliminary data in which we have demonstrated that the efficacy of
Temozolomide (TMZ), an established chemotherapeutic for glioblastoma (GBM) is substantially
modulated by the time of day when it is administered. These findings suggest that we may
already have the means of significantly improving outcome from this dismal disease. In this
proposal we will utilize novel intracranial xenograft models of GBM in which tumor cells have
been engineered to serve as reporters of tumor circadian time, and in which recipient mice have
been genetically engineered to represent four different patterns of diurnal variations in behavior,
or chronotype. We will test in vivo, whether GBM cells maintain stable circadian rhythms,
whether these are independent or entrained by the host, whether treatment with TMZ is best
optimized to tumor or host circadian rhythm and whether there is therapeutic value in ablating
tumor circadian rhythm. Success in these studies will advance our basic understanding of GBM
circadian biology and will provide critical information for the translational application of
chronotherapy to GBM care.

## Key facts

- **NIH application ID:** 10110184
- **Project number:** 1R21NS120003-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Erik Herzog
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2020-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110184

## Citation

> US National Institutes of Health, RePORTER application 10110184, Chronotherapy for glioblastoma (1R21NS120003-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10110184. Licensed CC0.

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