Canonical gliomagenesis mediators EGFR, P53, and retinoblastoma protein (RB1) are important for cancer signaling. Canonical gliomagenesis mediators EGFR, P53, and retinoblastoma protein (RB1) are important for cancer signaling. EGFR is amplified or mutated to the constitutively active EGFRvIII and propagates kinase signaling cascades to promote proliferation, invasion, and angiogenesis. P53 is a tumor suppressor that is mutated in GBM, allowing B-cell lymphoma 2 (BCL2) to inhibit apoptosis. RB is another tumor suppressor that, when inactivated, releases E2F transcription factor 1 (E2F1) to activate cell cycling and growth. Percentages of aberrations of commonly mutated genes (in yellow) are reported, determined from TCGA analysis of patient samples (Brennan et al., 2013). Andrea Shergalis et al. Pharmacol Rev 2018;70:412-445 Copyright © 2018 by The Author(s)‏