Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

Pharmaceuticals

Tebatso M. G. Boshomane¹  Thomas Ebenhan²  Julie Bolcaen³  Shankari Nair³  Charlot Vandevoorde³  Cathryn H. S. Driver⁴ 

[1] Department of Nuclear Medicine, University of Pretoria Steve Biko Academic Hospital, Pretoria 0001, South Africa;Pre-Clinical Imaging Facility, Nuclear Medicine Research Infrastructure, Pelindaba, Brits 0242, South Africa;Radiobiology, Radiation Biophysics Division, Nuclear Medicine Department, iThemba LABS, Cape Town 7131, South Africa;Radiochemistry, South African Nuclear Energy Corporation, Pelindaba, Brits 0240, South Africa;

关键词: targeted radionuclide therapy;    glioblastoma;    radiochemistry;    theranostics;    molecular imaging;    tyrosine kinases;   

DOI  :  10.3390/ph14070626

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown