Using extrinsic agents like TRAIL has two putative advantages over intrinsic agents: firstly, TRAIL can trigger apoptosis independently of p53, which is commonly mutated in primary (28%) and secondary (65%) GBM patients [19], contributing, in part, to TMZ resistance [20]; and secondly, TRAIL can kill cancer cells without conferring significant toxicity to normal cells [21, 22]. The gene discussed is TNFSF10; the disease is glioblastoma.