NCI Grant Will Help Assess New Treatment for Deadly Brain Tumor

Puduvalli

Sampath

The National Cancer Institute (NCI) has awarded a five-year grant of nearly $2.83 million to help a research team at the OSUCCC – James conduct a clinical trial that will assess a potential new treatment for patients with glioblastoma, a lethal primary brain tumor with limited treatment options.

The grant was awarded to a team led by co-principal investigators Vinay Puduvalli, MBBS, professor and director of the Division of Neuro-Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, and Deepa Sampath, PhD, assistant professor in the Division of Hematology at Ohio State and member of the Leukemia Research Program at the OSUCCC – James. Puduvalli also holds the Sanford and Rife Family Endowed Chair in Neuro-Oncology and serves as medical director of the Neurological Malignancies Service Line.

In their project abstract, Puduvalli and Sampath note that the current standard treatment for glioblastoma—chemotherapy with a drug called temozolomide combined with radiation therapy—yields a median survival of only 16-18 months, underscoring the need for novel therapies involving drugs that can overcome tumor resistance to chemotherapy and radiation therapy. 

In preclinical studies, the researchers have discovered that a drug called onalespib makes glioma cells more sensitive to temozolomide and radiation therapy, slowing glioma growth in animal models and extending their survival. The scientists explain that onalespib, which can cross the body’s natural blood brain barrier, works by blocking the activity of heat shock protein 90 (Hsp90), a protein complex that is critical for tumor cell survival and treatment resistance.

“Building on these promising results,” they write, “we will conduct a trial that will assess the benefit of blocking Hsp90 along with chemoradiation in malignant brain tumors.”

The phase I clinical trial will help the researchers identify the maximum tolerated dose of the Hsp90 inhibitor/chemoradiation combination in adults with newly diagnosed glioblastoma. The scientists also will conduct key correlative tissue and plasma studies.

The team believes this clinical trial “bears promise in providing a new treatment option for patients with glioblastoma as well as providing valuable new information related to whether the Hsp90 inhibitor used can block its targets in tumor tissue,” information that may be extended to other cancers for which the effects of this class of drugs are being explored.