It is known that DR4 and CASP8 are factors affecting the nonmitochondrial apoptotic pathway, and the loss of DR4 expression (which was shown to be mediated by promoter methylation) attenuates apoptosis and is associated with the resistance of glioma cells to proapoptotic ligand therapy (known as TRAIL resistance) [21]. The gene discussed is CASP8; the disease is central nervous system cancer.