# SPORE: Targeted Therapies for Glioma

> **NIH NIH P50** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $2,252,175

## Abstract

This is the competing renewal of a SPORE initiative on glioma at Dana-Farber/Harvard Cancer Center. Our
objective is to improve the standard of care for children, young adults, and adults with these tumors through
the use of targeted therapies. Towards this end, basic scientists from Harvard Medical School and the Broad
Institute join with clinical/translational investigators from Boston Children’s Hospital, Brigham and Women’s
Hospital, Dana-Farber Cancer Institute and Massachusetts General Hospital. There are four projects:
 Project One targets pediatric low-grade astrocytomas (PLGAs). Nearly 75% of PLGAs are driven by
activating mutations in the BRAF protein kinase. Clinician/scientists Daphne Haas-Kogan, M.D. and Karen
Wright, M.D. together with structural biologist Michael Eck, M.D., Ph.D. will develop and test brain-penetrant
targeted therapeutics for BRAF-mutant PLGAs. Project Two targets IDH-mutant gliomas which present
typically in young adults. IDH-mutant gliomas produce extraordinarily high levels of the ‘oncometabolite’ R-2-
hydroxyglutarate (2-HG). However, therapeutic exploitation of the differential 2-HG content between normal
and malignant brain tissue has yet to be realized. Neurosurgeon Daniel Cahill, M.D., Ph.D. and cancer
biologist William Kaelin, M.D. will address this therapeutic lacuna. Project Three targets adult gliomas.
Recent studies by basic scientist Jean Zhao, Ph.D. show that in addition to suppressing cell cycle progression,
CDK4/6 antagonists promote anti-tumor immunity and synergistically enhance the response to checkpoint
inhibitors. Going forward, Dr. Zhao together with neuro-oncologist Patrick Wen, M.D. will test the hypothesis
that brain penetrant CDK4/6 inhibitors can augment immunotherapeutic approaches to GBM. Project Four
targets the neuronal microenvironment of adult and pediatric gliomas. Neuro-oncologist and developmental
neurobiologist Michelle Monje, M.D., Ph.D. has shown that neurons promote glioma growth through activity-
regulated secretion of neuroligin-3 (NLGN3) into the tumor microenvironment. Basic scientist Mario Suva,
M.D, Ph.D. has refined methods for single cell sequencing of the multiple cell types within the
microenvironment of freshly resected human gliomas. Working together, Monje and Suva will define the
molecular mechanisms whereby microenvironmental NLGN3 modulates formation and progression of gliomas
and explore a novel therapeutic opportunity embedded within the NLGN3 requirement.
 Rigor and reproducibility of work conducted in the four projects will be fostered by cores for Pathology
and for Biostatistics and Computational Biology. An Administration core will enable and manage the
multiple consortium agreements and collaborative interactions between 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...

## Key facts

- **NIH application ID:** 10245083
- **Project number:** 5P50CA165962-08
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Tracy T Batchelor
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,252,175
- **Award type:** 5
- **Project period:** 2013-09-19 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245083

## Citation

> US National Institutes of Health, RePORTER application 10245083, SPORE: Targeted Therapies for Glioma (5P50CA165962-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10245083. Licensed CC0.

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