New Insights on Protein Linking Lung Cancer and Brain Metastasis

Researchers from McMaster University, in collaboration with the Cleveland Clinic and Case Comprehensive Cancer Center, have unveiled a significant connection between a protein traditionally associated with Alzheimer’s disease and the spread of lung cancer to the brain. This groundbreaking discovery, published on July 2, 2025, in *Science Translational Medicine*, reveals that the protein BACE1 plays a crucial role in the development of brain metastases in lung cancer patients, offering new avenues for potential treatment options.

BACE1, or Beta-site APP-cleaving enzyme 1, has long been recognized for its involvement in Alzheimer’s, where it contributes to the production of amyloid plaques in the brain. However, recent findings suggest its role extends beyond neurodegenerative diseases. According to Dr. Sheila Singh, director of McMaster’s Centre for Discovery in Cancer Research and senior author of the study, "We’ve always associated BACE1 with Alzheimer’s disease, so to find it playing a major role in lung cancer brain metastases is an important discovery. It’s a reminder that cancer can hijack biological pathways in ways we don’t yet fully understand."

The study employed a cutting-edge gene activation technique known as a genome-wide in vivo CRISPR activation screen, which enabled researchers to activate thousands of genes in lung cancer cells and observe their effects on tumor growth in mice. Notably, when BACE1 was activated, the likelihood of cancer cells invading the brain significantly increased. This finding is critical, as brain metastases occur in up to 40% of patients diagnosed with non-small cell lung cancer, one of the most common forms of the disease.

Furthermore, the research team has identified that existing Alzheimer’s drugs, specifically Verubecestat, which inhibits BACE1 activity, may be repurposed to address this urgent clinical challenge. In experiments, mice treated with Verubecestat exhibited fewer and smaller brain tumors and demonstrated increased survival rates. Despite earlier setbacks in Alzheimer’s clinical trials, where a Phase 3 study was discontinued in 2018 due to unfavorable risk-benefit assessments, the current findings suggest a potential new application for this drug in oncology.

Dr. Shideng Bao, a researcher from the Cleveland Clinic’s Department of Cancer Biology and a corresponding author on the paper, emphasized the importance of interdisciplinary research in uncovering new pathways for treatment. "This study highlights how interdisciplinary partnerships can lead to breakthroughs in understanding and treating devastating diseases like brain metastases. By identifying BACE1 as a key player in the spread of lung cancer to the brain, we’ve uncovered a promising new avenue for therapeutic intervention that could ultimately improve outcomes for patients."

The research was supported by various esteemed organizations, including the Boris Family Fund for Brain Metastasis Research, the Canadian Cancer Society, and the Canadian Institute of Health Research. As the scientific community continues to explore the implications of these findings, further investigations will be necessary to assess the effectiveness of repurposed therapies in preventing the spread of lung cancer to the brain.

In conclusion, this study not only expands the understanding of BACE1’s role in cancer biology but also opens new possibilities for the treatment of lung cancer, potentially improving survival rates for patients suffering from this aggressive disease. The ongoing collaboration between institutions highlights the critical need for innovative approaches in tackling complex health challenges such as cancer metastasis.