# Targeted Therapies for Glioma

> **NIH NIH P50** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $2,539,918

## Abstract

Project summary
This is the renewal application of a SPORE initiative from Dana-Farber/Harvard Cancer Center. We
focus on gliomas of children and young adults. Our objective is to develop therapies targeted to
oncogenic drivers and/or oncogene-induced vulnerabilities of these tumors. Towards these ends, basic
scientists join with clinician scientists from Boston Children’s Hospital, Brigham and Women’s Hospital,
Dana-Farber Cancer Institute and Massachusetts General Hospital. There are three projects:
 Project one targets pediatric low-grade gliomas (pLGGs). Nearly 75% of pLGGs are driven
by truncation/fusion variants of the BRAF protein kinase. The project one team has made significant
contributions to development of tovorafenib – a brain penetrant type 2 RAF inhibitor that is effective
on all common BRAF oncoproteins. For this renewal application, the goals of project one are to
reduce variability in response to RAF inhibitors such as tovorafenib and develop non-invasive “child
friendly” tools to predict children most likely to require (and respond to) these drugs. Project two
targets diffuse midline gliomas (DMGs) – the deadliest brain tumor of children. DMGs cannot be
cured by conventional therapeutic modalities and the prevalent oncogenic drivers are undruggable.
During the current funding period, the project two team has identified a synthetic lethal “addiction” to
the alternate end joining pathway for DNA repair (“alt-EJ”) and identified brain-penetrant drugs that
specifically target this pathway. Going forward, the goal of project two is to exploit alt-EJ repair
antagonists as targeted therapeutics for DMG. Project three addresses the early-stage (lower-
grade) IDH mutant gliomas (hereafter termed “IDHM”) of young adults. During the current funding
period, the project team identified synthetic lethal vulnerabilities for the more aggressive (WHO grade
4) IDHM gliomas. Going forward, the goal of project three is to integrate these synthetic lethal
therapeutic opportunities for grade 4 IDHM glioma into “the vorasidenib era” that has been opened by
the recent clinical studies on early stage (grade 2) IDHM gliomas of young adults.
 The study plan employs contemporary methods in structural biology, cancer genomics,
computer science and machine learning. Each project has a human endpoint, and two projects will
involve clinical trials. Rigor and reproducibility of work will be fostered by cores for Pathology and for
Biostatistics. An Administration core will enable and manage the multiple consortium agreements
and collaborative interactions Harvard Medical School, the four participating Harvard teaching
hospitals and facilitate clinical trials and imaging studies. Intellectual vigor within the program is
sustained and refreshed by annual Career Enhancement Awards to young investigators and by
annual Developmental Project Awards.

## Key facts

- **NIH application ID:** 10935600
- **Project number:** 2P50CA165962-11
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Tracy T Batchelor
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,539,918
- **Award type:** 2
- **Project period:** 2013-09-19 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935600

## Citation

> US National Institutes of Health, RePORTER application 10935600, Targeted Therapies for Glioma (2P50CA165962-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10935600. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*