Table 1.

Small molecule receptor tyrosine kinase inhibitors used in cancer therapy

Target	Molecules	Observations
EGFR	1st generation inhibitors: Gefitinib Erlotinib Lapatanib	They showed promising results in preclinical studies, but with mixed results in clinical trials [22–25]
	2nd generation inhibitors: Afatinib Dacomitinib	Both drugs were approved by the FDA Afatinib had limited activity in combination with temozolomide [33]
	3rd generation inhibitors: AZD 9291 AEE 788	AZD 9291 proved to have better activity and selectivity than the previous inhibitors The third-generation EGFR inhibitor AZD9291 overcomes primary resistance by continuously blocking ERK signaling in glioblastoma [36] AEE 788 also inhibits VEGFR [38]
	Others: Vandetanib Neratinib AG556	Vandetanib also inhibits VEGFR [39] AG556 had promising results when used in combination with radiotherapy [43]
PDGFR	Imatinib mesylate Tandutinib AG 1433 AG 1296	Imatinib showed no significant changes in the HGGs and especially GBM tumor growth [46] Better results were obtained in combination with hydroxyurea [47] Tandutinib had little effect [49] AG 1433 and AG 1296 used alone are rather effective [50, 51]
IGF-R	PQ 401 Picropodophyllin BMS 536924 BMS 754807 NVP-AEW 541 OSI 906 AG 1024	PQ 401, BMS 536924 and picropodophyllin suppressed the growth and migration of GBM cells GSK 1838705A and NVP-AEW541 induced apoptosis [63–67] OSI 906 and BMS 754807 had good results in vitro AG1024 had rather modest inhibition activity alone or in combination with radiotherapy [68]
VEGFR	Vatalanib Pazopanib Sunitinib Cediranib Thalidomide Cabozantinib SU 1498	Vatalanib enhances the antiangiogenic activity [54] Disappointing results were obtained for pazopanib in combination with lapatinib [57] No promising activity for GBM patients treated with sunitinib [58] Cediranib is an inhibitor of VEGFR, PDGFR, and c-kit [59] Thalidomide had a good effect as palliative drug in advanced secondary glioblastoma [60] Cabozantinib had good results both in vitro and in clinical trials [61, 62] SU1498 had a limited anti-tumor activity [51]

EGFR – epidermal growth factor receptor, PDGFR – platelet-derived growth factor receptor, IGF-R – insulin-like growth factor receptor, VEGFR – vascular endothelial growth factor receptor, FDA – Food and Drug Administration, ERK – extracellular signal-regulated kinases, HGGs – high-grade gliomas, GBs – glioblastomas, c-kit – transmembrane tyrosine kinase receptor