$12.5M Grant to Develop Targeted Glioma Therapies

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At Brigham and Women’s Hospital, Tracy Batchelor, MD, MPH, chair of the Department of Neurology, has received a Specialized Programs of Research Excellence (SPORE) award from the National Cancer Institute (NCI).

Dr. Batchelor co-directs the SPORE award along with Mario Suva, MD, PhD, of Massachusetts General Hospital (MGH). SPORE grants support multi-project research programs that aim to improve outcomes in various types of cancers. Dr. Batchelor was first awarded the $12.5M grant in 2013, and this new award will renew funding for another 5 years. It’s one of six brain cancer SPORE grants in the U.S.

Dr. Batchelor’s research project, “Targeted Therapies in Glioma,” studies gliomas across all age groups. Gliomas are the most common primary brain tumors, representing about 80 percent of malignant primary brain tumors. The SPORE grant funds four projects, each of which combines preclinical and clinical work. The preclinical research uses mouse models to study specific genes and molecular pathways in gliomas. The clinical trials then apply these findings in patients.

“This SPORE grant allows the Brigham and our colleagues at Boston Children’s Hospital, Dana-Farber Cancer Institute, and MGH to address unmet needs in neuro-oncology,” said Dr. Batchelor. “Gliomas are devastating tumors that affect both children and adults. Few glioma patients survive more than five years. The clinical trials that emerge from this grant could improve outcomes in patients with gliomas.”

To support these projects, the SPORE grant includes three central “cores” (pathology, biostatistics and administration) that provide resources, from tissue processing and statistical tools to administrative support. The grant also covers two programs that focus on career enhancement and developmental research. Funded projects in the developmental research program could one day become a full project in the SPORE.

Multiple Research Projects Aim to Develop Targeted Therapies

The SPORE research projects strive to develop targeted therapies against glioma on four distinct fronts. To accomplish this, each project targets a specific molecular alteration in gliomas in different age groups.

The first project is led by the Brigham’s chair of the Department of Radiation Oncology, Daphne Haas-Kogan, MD, and Michael Eck, MD, PhD, of the Dana-Farber Cancer Institute (DFCI). They are studying the BRAF gene in pediatric astrocytomas, the most common solid tumor in children. In collaboration with an industry partner, the Brigham-led team has developed a novel drug to inhibit BRAF. The drug is currently in clinical trials. In November 2020, Drs. Haas-Kogan and Eck presented the results of their trial on the first nine children at the annual Society for Neuro-Oncology meeting.

The second project is led by William Kaelin, MD, a Nobel-prize-winning cancer biologist at DFCI, and Daniel Cahill, MD, PhD, of MGH. With a focus on young adults, this project aims to exploit a mutation in the IDH-1 gene that occurs in many gliomas. “The IDH-1 mutation creates an Achilles heel in many gliomas,” said Dr. Batchelor. “We’re using various drugs to try to kill tumor cells by exploiting that Achilles heel.”

While the first two SPORE projects focus on children and young adults, the third and fourth projects investigate gliomas in adults. The third project is led by Patrick Wen, MD, of the Brigham and DFCI, and Jean Zhao, PhD, of DFCI. They’re using a targeted CDK4/6 inhibitor drug to eliminate tumor cells in glioblastomas, the most common malignant primary brain tumor. The CDK4/6 pathway is active in about 80 percent of glioblastomas. Drs. Wen and Zhao have found that inhibiting this pathway boosts the benefit of immunotherapy, which glioblastoma typically resists. Clinical trials are underway to study various combinations of CDK4/6 inhibitors with immunotherapies.

The fourth project is led by Michelle Monje-Deisseroth, MD, PhD, of Stanford Medicine, in coordination with Dr. Batchelor. This project targets the neuronal microenvironment of gliomas. “Within the last 5 to 10 years, we’ve learned that neuronal signaling can feed the growth of gliomas,” said Dr. Batchelor. “There are many pathways and molecules that do that. We’re focusing on one pathway called neuroligin-3.”

Dr. Batchelor notes that a key investigator on this project, Humsa Venkatesh, PhD, of Stanford Medicine, was recently recruited to the Brigham. She will start at the Brigham in 2021 to continue her work on neuronal signaling in gliomas.

The Clinical Services at Brigham Support SPORE Grant

The SPORE grant’s preclinical research culminates in clinical trials at the Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC). Many glioma patients who undergo brain surgery at the Brigham can be enrolled in one of the clinical trials in the SPORE grant. The Brigham has an active neurosurgical service, led by E. Antonio Chiocca, MD, PhD, a tumor specialist and chair of the Department of Neurosurgery.

“The Brigham’s clinical services are at the heart of the SPORE,” said Dr. Batchelor. “It’s important for a grant like this to have a large clinical practice in neuro-oncology.”

The Brigham’s combination of advanced technology, technical skill and clinical expertise puts the hospital in a unique position to carry out the SPORE grant. At the Brigham, the Advanced Multimodality Image Guided Operating (AMIGO) suite helps neurosurgeons map tumors in the operating room to safely remove tissue, making the Brigham a leader in image-guided neurosurgery. The Brigham collaborates with clinicians at DFCI to provide world-class care for patients at their joint Center for Neuro-Oncology.

The SPORE grant involves a large multidisciplinary and multi-specialty team of neuroscientists, neurologists, neurosurgeons, oncologists and radiation oncologists who specialize in both pediatric and adult care. The team also works with the other brain cancer SPOREs across the country. The clinical and research teams share the findings of their work during presentations at an annual research-focused retreat.

“The SPORE grant’s focus on targeted therapies will hopefully lead to improved patient outcomes for gliomas,” said Dr. Batchelor. “By developing targeted approaches to the genetic drivers of these tumors in clinical trials, we believe this research may impact patients of all ages with brain tumors.”

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