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Antagonist molecule discovered by St Catharine’s Biomedical Fellow in treatment for brain cancer

04.10.17 16:29

Glioblastoma are highly aggressive brain tumours that are associated with an extremely poor prognosis despite invasive surgery followed by concurrent radiation and chemotherapy. Malignancy is closely associated with their vascularisation and the interaction between glioblastoma-initiating cells that are similar to neural stem cells and endothelial cells, where a key signaling peptide, apelin, is highly expressed. Professor Robert Glen (Department of Chemistry) and Dr Anthony Davenport (EMIT) discovered the first competitive apelin receptor antagonist, MM54, and subsequently more potent and selective apelin antagonists.

In collaboration with Dr Julie Gavard (University of Nantes) and colleagues, in a paper published in Brain, MM54 has shown remarkable anti-cancer properties in models of glioblastoma. Apelin antagonists appear to suppress endothelial-mediated expansion of glioblastoma patient-derived cells with stem-like properties and suppresses tumour initiation and growth. MM54 was safe and effective in lengthening the survival of intracranially xenografted mice, with no reported side-effects. Importantly in this model, MM54 is synergistic with the current therapy temozolomide, and may have the potential to be used synergistically with the standard of care therapy.