Outlining involvement of stem cell program in regulation of O6-methylguanine DNA methyltransferase and development of temozolomide resistance in glioblastoma: An Editorial Highlight for 'Transcriptional control of O6 -methylguanine DNA methyltransferase expression and temozolomide resistance in glioblastoma' on page 780.

Glioblastoma is a malignant brain tumor that inevitably develops resistance to standard of care drug temozolomide (TMZ) due to a population of cells called cancer stem cells (CSCs). These cells utilize progenitor cell signaling programs and develop robust DNA repair machinery. In this editorial highlight we focus on stem cell regulation of TMZ resistance and discuss findings of Happold et al. () that outline direct transcriptional regulation of DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) in glioblastoma CSCs through NFkB activation. The authors found that cells cultured in CSC propagating conditions exhibit increase in MGMT expression when compared to adherent differentiated monolayer cells. This in turn increases resistance to standard of care drug temozolomide (TMZ) in these cells. NFkB activation was found to directly activate expression of MGMT in sphere cultured GBM CSC.