Abstract:
Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration
rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is
common in GB, which subsequently leads to the activation of many downstream pathways that
have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine
kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort
to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous
RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical
trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up
the scope for theranostic applications. In this review, the present status of RTKIs for the treatment,
nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven
tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph
receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the
TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their
potential to become new therapeutic GB radiopharmaceuticals.
