Swapnil R Mishra
Swapnil R Mishra
Mumbai
A groundbreaking study by University of Cincinnati researchers, led by Debanjan Bhattacharya, PhD, reveals a novel approach to enhance radiation therapy’s efficacy in treating lung cancer that spreads to the brain. The study, published in the journal Cancers, explores the potential of AM-101, a benzodiazepine analogue, in improving radiation therapy outcomes.
Lung cancer is the leading cause of cancer deaths in the United States, accounting for one in five cancer deaths. Non-small cell lung cancer (NSCLC) is the most common type, responsible for 80-85% of lung cancer deaths. Brain metastases occur in up to 40% of lung cancer patients, significantly reducing life expectancy.
According to the American Cancer Society, one in five cancer deaths reported in the United States is associated with lung cancer making it the primary cause of cancer death. Non-small cell lung cancer (NSCLC), is the most common kind of disease found in the majority of 80 per cent to 85 per cent of cancer deaths.
Similarly, as many as four in ten (up to 40%) of lung cancer patients develop brain metastases during the disease, significantly reducing life expectancy to an average of eight to 10 months post-diagnosis.
The current treatment approach for lung cancer with brain metastases includes surgical intervention, precise radiosurgery, and whole-brain irradiation for patients with widespread brain involvement (more than 10 metastatic lesions).
“Lung cancer brain metastasis is usually incurable, and whole brain radiation treatment is palliative, as radiation limits therapy due to toxicity,” said Bhattacharya, research instructor in the Department of Neurology and Rehabilitation Medicine in UC’s College of Medicine initial side effects and overcoming resistance to radiation are major challenges when treating brain metastases from lung cancer. This highlights the importance of new treatments which are less toxic and can improve the efficacy of radiation therapy, are less expensive, and can improve the quality of life in patients.”
Bhattacharya’s team investigated AM-101’s effect on NSCLC, discovering that it activates GABA(A) receptors, triggering autophagy and increasing radiosensitivity.
Researchers led by Bhattacharya at UC explored the potential of AM-101, a benzodiazepine analogue created by James Cook, a medicinal chemist from the University of Wisconsin-Milwaukee. However AM-101’s effect on non-small cell lung cancer was unknown.
AM-101 is a particularly useful drug in the context of brain metastases in NSCLC, Bhattacharya said, as benzodiazepines are known to be able to pass through the blood-brain barrier that protects the brain from potentially harmful invaders that can also block some drugs from reaching their target in the brain.
In studies using animal models of lung cancer brain metastases, researchers discovered that AM-101 enhances the effectiveness of radiation treatment and notably increases survival rates. Moreover, the medication was observed to decelerate the growth of primary NSCLC cells and brain metastases.
Besides enhancing the efficacy of radiation, the inclusion of AM-101 in radiation therapy could potentially enable the use of lower radiation doses. This, in turn, has the potential to decrease side effects and toxicity for patients, according to Bhattacharya. The team is currently focused on preparing for a Phase 1 clinical trial to evaluate the combination of AM-101 and radiation within the lungs for patients with lung cancer that has metastasized to the brain.
Bhattacharya initiated this study during their tenure in the former UC researchers Soma Sengupta and Daniel Pomeranz Krummel’s lab, who are currently located at the University of North Carolina at Chapel Hill. Bhattacharya acknowledges the guidance and teamwork with other professionals at UC and various academic research organizations throughout the United States.
The study’s findings suggest that AM-101 could:
– Improve radiation therapy outcomes
– Enable lower radiation doses, reducing side effects and toxicity
– Enhance the efficacy of radiation treatment
The team is currently focused on preparing for a Phase 1 clinical trial to evaluate the combination of AM-101 and radiation within the lungs for patients with lung cancer that has metastasized to the brain.
Bhattacharya acknowledges the collaborative effort between multiple teams and the support of the Department of Neurology and Rehabilitation Medicine.
“This study reflects the strong collaborative effort between multiple teams, and I am grateful for the overall support,” Bhattacharya said. “My father’s passing motivated me to work harder to complete this project, as he had known about my research and wanted to see me succeed.”
*Key Takeaways:*
– AM-101 enhances radiation therapy’s efficacy in treating lung cancer brain metastases
– Activates GABA(A) receptors, triggering autophagy and increasing radiosensitivity
– Potential to reduce side effects and toxicity
– Phase 1 clinical trial underway
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