"This is the first controlled trial of re-irradiation and the first performed in glioblastoma patients up to now. It was already known that APG101 might be an innovative approach for treating glioblastoma, but the size of the protein molecule was potentially too large to cross the protective bloodbrain barrier and target the tumour. Radiotherapy opens up this barrier and may therefore be an effective vehicle for this compound."
APG101 plays a major role in the blocking of the CD95/CD95L system. CD95 is a protein that acts as a receptor on the surface of cells. When this cell receptor binds with the CD95 ligand (CD95L) another protein it prompts the cell to die.
"Until 2008, it was thought that activating this system represented a potential strategy for treating glioblastoma," Prof Wick will explain. "But then it was realised that this made the cancer cells resistant to cell death and actually increased their ability to proliferate and spread to other tissues. Therefore, inhibition rather than activation is now considered a meaningful hypothesis to be tested, particularly in brain tumours."
The researchers found that patients with tumours expressing the CD95L protein had a worse prognosis than patients with tumours that did not express CD95L. However, CD95L-expressing tumours responded better to the APG101 combination treatment, with an overall survival of 11.5 months for these patients, compared to 8.2 months for patients without an active form of the protein.
"This also implies that CD95L would be one of the first predictive markers in neuro-oncology, which may help to define patie
|Contact: José Abad|
ECCO-the European CanCer Organisation