SHH and glioblastoma: The resistance of glioblastoma to radiotherapy is similarly complex (Figure 3) because of hypoxic niches that limit formation of the reactive oxygen species necessary for cell killing, hyperactivated DNA damage response machinery, and active cross-talk between TME populations via shared pathways (e.g., Wnt, Shh, Notch, c-Met, STAT3) [102,103,104].