To evaluate the role of RTK-AXL in acquired and intrinsic therapy resistance and to provide a robust rationale for future study designs of clinical trials investigating TKIs in GBM, we aim to: (i) characterize the regulation of RTK-AXL in response to RTX and temozolomide (TMZ) treatment, (ii) investigate whether endogenous RTK-AXL expression is related to therapy response; and (iii) evaluate if the co-administration of the AXL-specific TKI R428 to standard GBM therapy, consisting of TMZ and RTX, augments treatment effects. Here, AXL is linked to glioblastoma.