Anarchy or Respect the Hierarchy? The Complexity of Glioblastoma.

Glioma stem-like cells (GSC) in glioblastoma (GBM) structure tumor cells into a hierarchical organization and are postulated to be recalcitrant to conventional treatments, resulting in fatal relapse of the disease. A better understanding of these cells would be essential for meaningful and lasting treatments. In this issue of Cancer Research, Virolle and colleagues report a fascinating phenotype whereby the extracellular signal-regulated kinase (ERK) pathway regulates a mechanism of dedifferentiation of GBM cells into a stem-like state expressing markers of pluripotency through an EGFR-ERK-EGR1-dependent axis. This aptly termed "toggle switch" may contribute to maintenance of GSCs, promote intratumor heterogeneity, and potentially provide innovative treatment options.See related article by Almairac et al., p. 3236.