Researchers at McMaster University, Cleveland Clinic, and Case Comprehensive Cancer Center have made a groundbreaking discovery that could reshape the treatment of lung cancer. They have identified a protein, previously associated with Alzheimer’s disease, that plays a crucial role in the spread of lung cancer to the brain. This finding, published in Science Translational Medicine on July 2, 2025, suggests that existing Alzheimer’s medications might be repurposed to prevent this deadly progression.
The study focuses on the protein BACE1, which is instrumental in the development of brain metastases—tumors that migrate to the brain from cancers originating elsewhere in the body. These metastases affect up to 40 percent of patients with non-small cell lung cancer, a significant portion of the cancer patient population.
The Role of BACE1 in Cancer Spread
Senior author Sheila Singh, director of McMaster’s Centre for Discovery in Cancer Research, emphasized the significance of this discovery. “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,” Singh stated. “It’s a reminder that cancer can hijack biological pathways in ways we don’t yet fully understand.”
To uncover this connection, researchers employed a cutting-edge technique known as a genome-wide in vivo CRISPR activation screen. This method allowed them to systematically activate thousands of genes in lung cancer cells and observe the effects in mice. When BACE1 was activated, the cancer cells showed a heightened propensity to invade the brain.
Potential for Repurposing Alzheimer’s Drugs
BACE1 has been long linked to Alzheimer’s disease, where it contributes to the formation of sticky plaques in the brain by cutting a protein called APP. However, its newfound role in cancer spread opens the door to novel therapeutic strategies. Researchers are particularly hopeful about the potential of Verubecestat, a drug initially developed to block BACE1 activity in Alzheimer’s patients.
In preclinical trials, mice treated with Verubecestat exhibited fewer and smaller tumors and enjoyed longer lifespans. Although a Phase 3 clinical trial for Alzheimer’s was discontinued in 2018 due to concerns over its benefit-risk profile, its application in cancer treatment remains promising.
“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 noted.
Implications and Future Research
While the discovery is promising, Singh and her colleagues caution that further research is necessary to fully understand the effectiveness of this therapy in preventing lung cancer’s spread to the brain. The study underscores the importance of interdisciplinary collaboration in addressing complex medical challenges.
“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. “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 team, which includes world leaders in brain cancer research, has previously identified pathways used by cancer cells to infiltrate the brain and developed new therapeutic approaches. This latest study was supported by numerous prestigious organizations, including the Boris Family Fund for Brain Metastasis Research, the Canadian Cancer Society, and the Cancer Research UK Lung Cancer Centre of Excellence.
Looking Ahead
The discovery of BACE1’s role in lung cancer brain metastases represents a significant step forward in cancer research. By potentially repurposing Alzheimer’s drugs, researchers hope to offer new hope to patients facing limited treatment options. As further studies are conducted, the medical community remains optimistic about the potential for improved patient outcomes and the development of more effective therapies.
