Combination Therapy Halts Repair Mechanism in Brain Tumors

Radiotherapy and panobinostat show promise treating glioblastoma.

The combination of radiotherapy and panobinostat can prevent cancerous cells in brain tumors from repairing themselves, a recent study found.

Radiotherapy has the ability to treat brain tumors by damaging them. However, cancer cells are able to mend, allowing them to keep living.

In order to address this issue, scientists looked into the histone deacetylase inhibitor panobinostat, which was approved in 2015 to treat patients with multiple myeloma. It is also being tested in other types of cancers.

This inhibitor is able to modify expression of approximately 8% of RNA molecules produced from genes. The modification of RNA causes protein production to change, leading to the unsetting of cancer growth. It also has the ability to turn off the DNA repair enzyme RAD51.

"We saw synergy between radiotherapy and the agent, panobinostat,” said senior study author Yaacov R. Lawrence, MD. “Our findings suggest panobinostat makes radiotherapy much more effective.”

The study enrolled 12 patients who were tested for gliomas, which showed high grade gliomas that recurred after initial radiotherapy. Currently there are about 10,000 patients diagnosed with gliomas each year. Glioblastoma and anaplastic astrocytoma represent nearly 70% of newly diagnosed patients with gliomas.

Within the study, 8 patients had recurrent glioblastoma, while 4 had recurrent anaplastic astrocytoma. Although patients initially responded to treatment, a majority of patients relapsed within 2 years with an overall survival rate of a year or less.

"There is no standard treatment for recurrent high grade gliomas,” said co-author Adam Dicker, MD, PhD, FASTRO. “At Jefferson, we have a lot of experience with offering a second course of radiation after a patient relapses, in order to increase survival, but we are excited by the promise of a targeted agent that makes initial and repeat radiotherapy more effective."

The highest dose of panobinostat was found to be well tolerated among patients, with an improvement seen in progression free survival and the overall survival rate.

"The intent of this study was not to demonstrate benefit of the combination therapy, but to test safety,” Lawrence said. “Still, we did note promising activity, which must be validated in further studies."