Given hypoxia-related EGFR signaling in GBM and sphingomyelin’s reduction in EGFR signaling, temozolomide (TMZ) in combination with an inhibitor of SPHK1 was assessed in a preclinical 3D spheroid GBM model by Sousa et al. This combination decreased GBM spheroid invasion and reduced the self-renewal capability of glioma stem cells (GSCs) especially under hypoxia, reversing hypoxia-induced resistance to chemotherapy [88]. Here, EGFR is linked to central nervous system cancer.