Fig. 4.

Intratumoral heterogeneity in GBM is a direct consequence of predictable cellular biomes driven by evolutionary progression. A summary of our findings is presented, demonstrating that observed molecular subtypes in GBM are directly influenced by regional changes in the tumor microenvironment. In addition, a summary of key molecular events driving individual cell biomes is provided, including global transcriptional repression and activation of growth factor signaling and cell cycle progression driving proliferation in the central tumor, to global transcriptional activation and increases in angiogenesis and reliance on glycolysis in the perinecrotic region. Therefore, combinatorial strategies designed to target these biomes individually may be important to further clinical advancement in GBM.