Treatment for
glioblastoma consists of
radiotherapy and
temozolomide-based
chemotherapy. However, virtually all patients recur, leading to a fatal outcome.
Receptor tyrosine kinase (RTK)-targeted
therapy has been the focus of attention in novel treatment options for these patients. Here, we compared the efficacy of
imatinib,
sunitinib, and
cediranib in
glioblastoma models. In the present work, the
biologic effect of the drugs was screened by viability, cell cycle, apoptosis, migration, and invasion in vitro assays or in vivo by chick chorioallantoic membrane assay. Intracellular signaling was assessed by Western blot and the RTK targets were identified using phospho-RTK arrays. The amplified status of KIT, PDGFRA, and VEGFR2 genes was assessed by quantitative polymerase chain reaction. In a panel of 10
glioblastoma cell lines, we showed that
cediranib was the most potent. In addition,
cediranib and
sunitinib synergistically sensitize the cells to
temozolomide.
Cediranib efficacy was shown to associate with higher
cytostatic and unique cytotoxic effects in vitro and both antitumoral and antiangiogenic activity in vivo, which could associate with its great capacity to inhibit
mitogen-activated protein kinase (MAPK) and AKT pathways. The molecular status of KIT, PDGFRA, and VEGFR2 did not predict
glioblastoma cell responsiveness to any of the RTK inhibitors. Importantly, phospho-RTK arrays revealed novel targets for
cediranib and
sunitinib therapy. In conclusion, the novel targets found may be of value as future
biomarkers for
therapy response in
glioblastoma and lead to the rational selection of patients for effective molecular targeted treatment.