New research led by University of Cincinnati researchers has identified a potential new way to improve outcomes for patients with lung cancer that has spread to the brain. Lung cancer is the leading cause of cancer death in the United States, with non-small cell lung cancer (NSCLC) being the most prevalent type. Brain metastases occur in up to 40% of lung cancer patients, with current standard treatments including surgical resection and stereotactic brain radiosurgery. However, whole brain irradiation is often necessary for patients with multiple brain lesions, leading to toxicity and limiting therapy. The study focused on AM-101, a benzodiazepine drug that can pass through the blood-brain barrier, activating GABA(A) receptors in NSCLC cells and promoting the autophagy process, making cancer cells more sensitive to radiation.
The team’s research showed that AM-101 activates GABA(A) receptors in lung cancer cells, increasing the expression of GABARAP and Nix, which enhances the autophagy process and makes the cells more responsive to radiation treatment. In animal models, AM-101 was found to improve the effectiveness of radiation therapy and significantly extend survival rates. In addition to enhancing radiation therapy, AM-101 may also allow for lower radiation doses, potentially reducing side effects and toxicity for patients. The team is now working towards opening Phase 1 clinical trials to test the combination of AM-101 and radiation in lung cancer patients.
Debanjan Bhattacharya, the lead author of the study, credits his mentors and collaborators for the success of the research, highlighting the importance of shared university research resources in advancing their findings. Bhattacharya dedicated this work to his father, who passed away during the early stages of the research, motivating him to work harder to complete the project. The study was conducted at the University of Cincinnati and involved collaborations with experts from multiple academic institutions across the United States. The team’s findings have the potential to revolutionize the treatment of lung cancer brain metastases, offering a less toxic and more effective alternative to current therapies.
Lung cancer brain metastasis is typically incurable, with current whole brain radiation treatments being palliative in nature. The development of AM-101 as a potential therapeutic agent for enhancing radiation therapy represents a significant advancement in the field. By targeting GABA(A) receptors and promoting autophagy in lung cancer cells, AM-101 has the potential to make radiation treatment more effective while reducing the side effects associated with higher radiation doses. The team’s collaboration with other experts and use of shared research resources at the University of Cincinnati were instrumental in advancing this groundbreaking research.
The study’s results highlight the promising potential of AM-101 in improving outcomes for patients with lung cancer brain metastases. By amplifying the cells’ sensitivity to radiation therapy, AM-101 has the ability to enhance treatment efficacy and extend survival rates for these patients. With ongoing efforts to initiate clinical trials testing the combination of AM-101 and radiation therapy in lung cancer patients, the team is on track to bring this innovative treatment approach to the forefront of cancer care. The dedication and collaborative efforts of the researchers, along with the mentorship and support of their institutions, have been key in pushing this research forward and bringing it one step closer to clinical application.