Welcome to a look at a remarkable scientific breakthrough from the University of Pennsylvania that has illuminated an entirely unexpected therapeutic potential for hydralazine in treating glioblastoma, one of the most aggressive and lethal forms of brain cancer. For more than seven decades, hydralazine, an old blood pressure drug (Apresoline), has been a vital vasodilator on the World Health Organization’s List of Essential Medicines. Yet, the precise molecular target responsible for its effects remained an enduring pharmacological mystery until now.
This episode delves into how researchers unveiled the mechanism by which this widely available medication may possess the remarkable ability to “silence” tumor growth. The team identified 2-aminoethanethiol dioxygenase (ADO enzyme) as the drug’s highly selective molecular target. ADO functions as a critical oxygen sensor within cells, and its elevated expression is associated with the malignancy grade of glioblastoma tumors. By blocking ADO, hydralazine prevents the degradation of regulatory proteins (like RGS4 and RGS5).
Critically, when glioblastoma cells are treated with hydralazine, they undergo cellular senescence, a stable, irreversible growth arrest, rather than cell death. This discovery validates the potential of drug repurposing to offer hope where few treatment options exist, especially considering that the current standard of care for glioblastoma has remained largely unchanged since 2005.
We explore the significant advantages of repurposing, including leveraging hydralazine's well-characterized seven decades of clinical safety data, and the major obstacle: the difficulty of getting the drug to cross the blood-brain barrier (BBB) to reach the tumor. The research provides an invaluable molecular blueprint for developing new, brain-penetrant derivatives.
Please note: This research is entirely experimental and investigational. No clinical trials have yet evaluated hydralazine specifically for brain cancer treatment in human patients, and patients should not alter their prescribed regimens without consulting their medical team. The path from laboratory discovery to clinical application is likely to require 5–10 years of additional research.