Parkinson's Drug Found Effective Against Brain Metastasis in Breast Cancer

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Parkinson’s Drug Found Effective Against Brain Metastasis in Breast Cancer

Parkinson’s Drug Found Effective Against Brain Metastasis in Breast Cancer

Researchers have discovered that a discontinued drug originally used to treat Parkinson’s disease symptoms might be effective in treating metastatic breast cancer, particularly the brain metastases it often leads to. This repurposed drug has the potential to become a novel therapy in the fight against cancer.

Breast cancer is a leading cause of brain metastasis, and it is also the most common cause of cancer-related death in women worldwide. Brain metastases in breast cancer are challenging to treat because the body’s protective blood-brain barrier (BBB) typically prevents drugs from penetrating and killing cancer cells.

In a recent study, researchers at Northwestern University Feinberg School of Medicine in the United States have been on the quest for a drug that can penetrate the blood-brain barrier and effectively kill cancer cells. It appears they may have struck gold.

The project’s lead author, Jawad Fares, commented, “The significance of this project lies in its potential to address an urgent clinical challenge: the treatment of brain metastasis, particularly in breast cancer. It offers hope for improving the quality of life and survival outcomes for a significant number of patients with brain metastases, a common and serious complication of cancer. The identification of the novel therapeutic drug metixene and insights into its mechanism add a promising dimension to cancer research and treatment.”

Researchers screened over 320 FDA-approved small-molecule central nervous system inhibitors known to penetrate the BBB. Among the tested drugs, metixene, a discontinued drug previously used to treat Parkinson’s disease symptoms, emerged as the top candidate for killing various subtypes of metastatic breast cancer and brain metastasis cancer cells.

Parkinson's Drug Found Effective Against Brain Metastasis in Breast Cancer

Injecting metixene into mice not only reduced the size of breast cancer tumors but also extended the lifespan of mice with multi-organ metastasis and single or multiple brain metastases.

Researchers observed that metixene induced cancer cells to undergo incomplete autophagy (accumulation of cellular “garbage” that cannot be recycled and reused) by activating the NDRG1 protein, leading to cell death or apoptosis. Knocking out the NDRG1 gene using CRISPR-Cas9 gene editing technology resulted in complete autophagy and the reversal of apoptotic effects.

Fares said, “This research underscores the potential clinical significance of metixene as a treatment drug for metastatic cancers and brain metastatic tumors. Reportedly, this drug has minimal side effects on the human body, making it a strong candidate for clinical translation, which means further research and potential use in clinical trials.”

The study has been published in “The Journal of Clinical Investigation.”