In Australia, brain cancer is the leading cause of cancer-associated death for adults under the age of 40 and children under the age of 10, with one person dying every eight hours. The most common brain tumour is glioblastoma. The standard of care for glioblastoma patients (surgery, radiation and chemotherapy) is the only therapeutic option, and one that is never curative. For patients receiving this treatment the 5-year survival rate is less than 5%, with the vast majority succumbing to the disease within two years. Thus, the need for new therapeutic strategies is urgent.
We are developing a promising new strategy involving degradation of the protein called EGFR. 60% of glioblastoma patients will present over-expression of EGFR, which drives the aggressive tumour growth. Drugs that turn EGFR off are approved for other cancers, but have failed in glioblastoma trials thus far. Recent evidence suggests that to treat brain tumours, it is necessary not only to turn EGFR off, but also to remove the protein itself. A novel and unique way to do this is by turning off another protein called DYRK1A using DYRK1A-targeting drugs.
In preliminary work for this project we demonstrated that the combination of DYRK1A- and EGFR-targeting drugs kills glioblastoma cells while sparing healthy cells. With the funding received from the Brain Foundation we will now be able to generate significant evidence necessary to progress this new treatment option to clinical trials.
The outcomes of this first ever evaluation of a novel drug combination will have profound implications for glioblastoma patients. This project will open up the possibility of improving survival of glioblastoma patients using DYRK1A-targeting drugs that have already been identified and are now in clinical development. As a result, translation of the preclinical evidence generated by this project could be achieved in the near future.