Considering that conclusions about promoter methylation based on four GBM cell lines may not fully capture the heterogeneity of primary and recurrent GBM including in their circadian gene expression [22–24] and the clinical challenges posed by repeating biopsies at multiple times of day, approaches like focused ultrasound-enhanced liquid biopsies, ex vivo organotypic patient-derived slice cultures, or patient-derived tumor spheroids could accurately and less-invasively measure daily MGMT expression and promoter methylation in individual patient samples [21, 25, 26]. This evidence concerns the gene MGMT and glioblastoma.