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Researchers from the University of Cincinnati have discovered a promising approach to improve radiation treatment for patients with metastatic lung cancer, potentially offering better outcomes for those battling this aggressive form of the disease. The study, led by Debanjan Bhattacharya, PhD, and published in the Cancers journal, highlights how the drug AM-101 could significantly enhance radiation therapy for non-small cell lung cancer (NSCLC) patients whose cancer has spread to the brain.
Lung cancer remains the leading cause of cancer-related deaths in the United States. Of particular concern, approximately 40% of patients with lung cancer experience metastasis to the brain, and most survive for less than a year, even with treatment. While surgical and radiation treatments can help, they often only provide relief from symptoms, with significant risks of side effects, such as toxicity. Bhattacharya’s team has identified AM-101, a benzodiazepine analog, as a potential way to enhance radiation’s effects and reduce the associated toxicity.
AM-101 works by activating GABA(A) receptors in lung cancer and brain metastatic cells. This activation triggers autophagy, a process where cells break down and recycle unwanted components, making them more vulnerable to radiation. The study revealed that enhancing autophagy in NSCLC cells improves the effectiveness of radiation. In animal models of brain metastases, AM-101 not only improved survival but also slowed the growth of both primary lung tumors and brain metastases. Importantly, AM-101's ability to cross the blood-brain barrier makes it especially useful in treating brain metastases, a challenge with many conventional therapies.
In addition to enhancing the impact of radiation, AM-101 may allow for lower radiation doses, thereby reducing the severe side effects typically associated with brain irradiation. The development of this drug combination could lead to better treatment outcomes and improve the quality of life for patients with metastatic lung cancer. With Phase 1 clinical trials on the horizon, this research marks an important step toward more effective and less toxic treatments for lung cancer patients and underscores the importance of collaborative efforts in advancing cancer care.