Lung cancer is the leading cause of cancer-related deaths in the U.S., responsible for about one in five cancer deaths, according to the American Cancer Society. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of lung cancer cases, making it the most common type of the disease.

A research team from the University of Cincinnati, led by Dr. Debanjan Bhattacharya, has found a potential new way to enhance radiation therapy's efficacy and improve outcomes for patients whose lung cancer has metastasized to the brain. Their findings were recently published in the journal Cancers.

Up to 40% of lung cancer patients develop brain metastases, with an average survival rate of 8 to 10 months following diagnosis. Current treatments for brain metastases from lung cancer include surgical resection, stereotactic brain radiosurgery, and whole brain irradiation. However, these therapies are often palliative due to radiation toxicity.

"Lung cancer brain metastasis is typically incurable," said Bhattacharya. He emphasized the need for new treatments that are less toxic and more effective, improving both therapy outcomes and patients' quality of life.

The study focused on AM-101, a synthetic analog in the benzodiazepine drug class developed by medicinal chemist James Cook at the University of Wisconsin-Milwaukee. Previously, AM-101’s effect on NSCLC was unknown. The team found that AM-101 activates GABA(A) receptors in NSCLC cells, triggering autophagy—where the cells recycle and degrade unwanted parts. This enhanced autophagy makes lung cancer cells more sensitive to radiation.

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Animal models showed that combining AM-101 with radiation significantly improved survival rates and slowed the growth of both primary lung cancer and brain metastases. This approach could also allow for lower radiation doses, reducing side effects and toxicity.

The team is now working toward Phase 1 clinical trials to test this combination in both lung cancer and lung cancer metastasized to the brain.

Dr. Bhattacharya began this research while working with former UC researchers Soma Sengupta and Daniel Pomeranz Krummel, now at the University of North Carolina at Chapel Hill. Bhattacharya credits their mentorship and the collaborative support of multiple research institutions. He dedicated this study to his father, who passed away in 2021 during the early stages of the research, motivating him to complete the project.