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Figure 7. Overview of mechanisms involved in TMZ resistance in GBM. The molecular mechanisms contributing to TMZ resistance in GBM are nuanced and extensive yet fall primarily into the fundamental categories of DNA repair, cell stemness, HDAC activity, aberrant receptor and transcription factor activity, autophagy, activation and suppression by various miRNAs, and intercellular transport of oncogenic factors via extracellular vesicles. There is significant interplay between all of these categories, and often a mutation or overactivation in one category will prompt or amplify additional resistance pathways. For this reason, successful combating of TMZ resistance will require a multifaceted approach that prevents compensation through alternative resistance mechanisms. GBM: glioblastoma; TMZ: temozolomide; HDACs: histone deacetylases