# Novel genetic dependencies in VRK2 methylated glioblastoma multiforme

> **NIH NIH R03** · DANA-FARBER CANCER INST · 2020 · $178,000

## Abstract

Abstract
Glioblastoma multiforme (GBM) affects 10,000 Americans each year and is one of the most common and
deadly brain cancers, with a median overall survival of 12-14 months from diagnosis. Treatment consists of a
surgical resection, followed by chemo-radiation and further rounds of chemotherapy. In particular, patients
whose tumors harbor MGMT methylation exhibit better responses to temozolomide (TMZ). Despite advances
in care, few patients survive more than 5 years, and new treatments are desperately needed.
We have created and interrogated the Cancer Dependency Map (www.depmap.org) and have discovered that
a subset of GBM cell lines require VRK1 for proliferation and survival. Cancer cell lines that depend on VRK1
exhibit methylation and down-regulation of VRK2, a kinase involved in the DNA damage response and mitotic
chromosome segregation. In the TCGA GBM cohort, approximately 15% of patients show decreased
expression of VRK2.
We propose to confirm VRK1 dependency in cancer cell lines and patient-derived GBM organoids with VRK2
methylation, and will determine whether VRK1 loss leads to defects in chromosome segregation and DNA
damage response. In parallel, we will use a global phospho-proteomic approach to discover other druggable,
signaling pathways affected by VRK2 methylation. Taken together, these studies will credential VRK1 as a
target in GBM that exhibit VRK2 methylation and form the foundation for drug development efforts focused on
the VRK family of kinases.

## Key facts

- **NIH application ID:** 10046375
- **Project number:** 1R03TR003343-01
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** William C. Hahn
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046375

## Citation

> US National Institutes of Health, RePORTER application 10046375, Novel genetic dependencies in VRK2 methylated glioblastoma multiforme (1R03TR003343-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10046375. Licensed CC0.

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