(Press-News.org) Researchers at McMaster University, Cleveland Clinic and Case Comprehensive Cancer Center have uncovered how a protein long associated with Alzheimer’s disease helps lung cancer spread to the brain – a discovery that offers hope that existing Alzheimer’s drugs could be repurposed in preventing cancer’s spread.
The study, published in Science Translational Medicine on July 2, 2025, details how the protein (BACE1) is instrumental in the development of brain metastases – tumours that spread to the brain from cancers originating elsewhere in the body – in people with lung cancer. These tumours occur in up to 40 per cent of patients with non-small cell lung cancer.
“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,” says senior author Sheila Singh, director of McMaster’s Centre for Discovery in Cancer Research and professor with the Department of Surgery. “It’s a reminder that cancer can hijack biological pathways in ways we don’t yet fully understand.”
To make the discovery, researchers used a cutting-edge gene activation technique known as a genome-wide in vivo CRISPR activation screen. The technique allowed researchers to systematically activate thousands of genes one by one in lung cancer cells and put the modified cells into mice. When BACE1 was switched on, the cancer cells were far more likely to invade the brain.
BACE1 has long been linked to Alzheimer’s disease, the most common form of dementia. In people with Alzheimer’s, BACE1 cuts a protein called APP, triggering the formation of sticky plaques in the brain.
Currently, there are limited therapies available once cancer has spread to the brain. However, researchers say the discovery of BACE1 does offer hope as a drug developed for Alzheimer’s could be repurposed.
The therapy uses a drug called Verubecestat that blocks BACE1 activity. Researchers found that mice given Verubecestat had fewer and smaller tumours, and also lived longer. The drug had shown promise in Alzheimer’s patients but a Phase 3 clinical trial was discontinued in 2018 after a committee determined it was unlikely that positive benefit/risk could be established.
“The discovery of BACE1 opens the door to repurposing existing treatments like Verubecestat to potentially prevent or slow the spread of lung cancer to the brain, where treatment options are currently very limited,” Singh says.
The team say more research is needed to better understand the effectiveness of the therapy in preventing the spread of lung cancer to the brain.
“This study highlights how interdisciplinary partnerships can lead to breakthroughs in understanding and treating devastating diseases like brain metastases,” said Shideng Bao, a researcher in Cleveland Clinic’s Department of Cancer Biology, a corresponding author on the paper. “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 Sheila Singh Lab collaborated with Cleveland Clinic and Case Comprehensive Cancer Center on the research. Singh and her colleagues are world leaders in brain cancer research, previously discovering a pathway used by cancer cells to infiltrate the brain, as well as new therapeutic approaches.
The study was supported by funding from the Boris Family Fund for Brain Metastasis Research, the Canadian Cancer Society, the Canadian Institute of Health Research, the Cancer Research UK Lung Cancer Centre of Excellence the Cleveland Clinic Foundation and Lerner Research Institute, and a Sir Henry Wellcome Fellowship.
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Interested in covering this research?
Senior author Sheila Singh, director of McMaster’s Centre for Discovery in Cancer Research and professor with the Department of Surgery, can be reached directly at ssingh@mcmaster.ca.
For any other information, contact Adam Ward, media relations officer with McMaster University’s Faculty of Health Sciences at warda17@mcmaster.ca.
END
Scientists discover protein that helps lung cancer spread to the brain
2025-07-02
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