Northwestern MedicineNovel Therapy Extends Survival in Metastatic Cancer

Metixene: A New Frontier in Metastatic Breast Cancer and Brain Metastasis Treatment

Northwestern Medicine researchers have made a groundbreaking discovery in the treatment of metastatic breast cancer and brain metastases. Their recent study in the Journal of Clinical Investigation unveils metixene, a central nervous system small-molecule inhibitor, as a potent therapeutic agent. This advancement promises significant implications for the quality of life and survival outcomes in patients suffering from these severe cancer complications.

Key Points

• Innovative Treatment: Metixene, originally an antiparkinsonian drug, has been identified as effective in treating metastatic breast cancer and brain metastases.
• Research Leadership: The study was led by Maciej Lesniak, MD, with notable contributions from a team of experts at Northwestern Medicine.
• Mechanism of Action: Metixene induces cancer cell death by triggering ‘incomplete autophagy’, a process where waste accumulation leads to cellular self-destruction.
• Protein Activation: The drug works by activating the NDRG1 protein, which is crucial in inducing cancer cell death.
• CRISPR-Cas9 Insights: Gene editing experiments reveal that knocking out NDRG1 reverses metixene-induced apoptosis in cancer cells.
• Clinical Significance: Minimal side effects and the ability to cross the blood-brain barrier make metixene a strong candidate for future human clinical trials.
• Broad Screening: More than 320 FDA-approved drugs were screened before identifying metixene as a top candidate.
• Impact on Survival: Metixene not only reduced tumor size but also increased lifespan in mice with breast cancer metastases.
• Multi-Organ Efficacy: The drug was effective against multi-organ site metastases and multiple brain metastases in animal models.
• Global Context: Breast cancer, a leading cause of cancer-related death in women worldwide, often leads to brain metastases, underscoring the significance of this discovery.

“The identification of a novel therapeutic agent, metixene, and its mechanistic insights add a promising dimension to the field of cancer research and treatment.”
– ​Jawad Fares, MD, MSc, Lead Author and Neurosurgery Resident and Postdoctoral Fellow in the Lesniak Laboratory

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