The epidermal growth factor receptor (EGFR) is altered in 50% of glioblastomas (GBMs), but EGFR inhibitors have yielded disappointing results in clinical assays. A new study may allow improved targeting of EGFR-dependent GBMs by identifying a key regulator of EGFR in GBMs (J. Clin. Invest. http://dx.doi.org/10.1172/JCI63623).

Natividad Pozo et al. examined the effect of DYRK1A, a kinase important in central nervous system development, on EGFR in established GBM cell lines. They found that silencing of DYRK1A led to a reduction in the amounts of EGFR and inhibited self-renewal of the cells. Downregulation of DYRK1A also decreased tumor growth in nude mice after injection of GBM cells. Similarly, the authors found that pharmacological inhibition of DYRK1A reduced self-renewal of GBM cells and decreased tumor growth in nude mice injected with GBM cells.

The researchers then turned their attention to human glioma samples, finding that DYRK1A was more highly expressed in gliomas compared with normal brain tissue. They also identified a positive correlation between EGFR and DYRK1A expression in GBM samples.

Notably, the authors' data indicate that DYRK1A acts at the level of regulating EGFR stability rather than its kinase activity. They suggest that targeting DYRK1A, either alone or in combination with EGFR inhibitors, could have therapeutic benefit in EGFR-dependent GBMs.