A new study has identified a more precise and effective way to prevent cancer from spreading to the brain.
The paper, published in the Proceedings of the National Academy of Sciences (PNAS), details the development of novel drug candidates that target a key enzyme implicated in the spread of lung, breast, skin, and other cancers to the brain. The work builds on a promising new therapeutic strategy first reported by the same group of researchers last year.
The new drug candidates are designed to intercept rogue cancer cells before they depart other primary tumours and ultimately travel toward the brain.
Lead author Professor Sheila Singh, based at both King's College London and McMaster University, says that this type of cancer - called metastatic brain cancer - is the most common type of brain tumour in adults and comes with an extremely grim outlook, with 90 per cent of patients passing away within just one year of diagnosis.
The current treatment paradigm is largely palliative, she adds, which is why her group is focusing instead on developing preventative interventions.
By identifying patients who are at high risk of developing this type of brain cancer and trying to intercept the metastasising cells before they can even form a brain tumour, we can transform this fatal disease into one that is entirely preventable."
Sheila Singh, Professor of Neuro-oncology and Neurosurgery at King's College London and McMaster University
The new therapeutics, which are being developed by McMaster spin-out company Block Biosciences, target an enzyme called IMPDH2, which plays a critical role in the development of brain metastases.
IMPDH has long been explored as a druggable target in cancer research, and some drug candidates have even advanced as far as human trials; however, drugs that block IMPDH have historically caused significant side effects because they also inhibit healthy cells.
But Singh's group is targeting IMPDH2 - one of two forms of the enzyme that is vital to the cells that start brain metastases. But, unlike its other form, IMPDH2 is not abundant in healthy tissue, indicating that drugs that target IMPDH2 selectively will eliminate rogue cancer cells without causing major side effects.
Taking a highly selective approach to eliminating these cancer-initiating cells allows us to strike the right balance between effectiveness and safety."
Agata Kieliszek, a postdoctoral fellow at McMaster and head of biology and operations at Block Biosciences
Drug development is now underway, jointly led by medicinal chemists at McMaster and Block. The collaborative research team has already designed and synthesized several hundred IMPDH2-targetting drug candidates and are selecting the best of these compounds to advance further down clinical development pathways.
