title: Some implications of receptor kinase signaling pathway for development of multitargeted kinase inhibitors.
abstract: Epidermal growth factor receptors (EGFRs) belong to the ErbB family of receptor tyrosine kinases (TKs). Based on the role of EGFR signaling pathway in malignant progression of various types of tumors, a growing interest in the use of EGFR-TK inhibitors as probes for molecular imaging of EGFR-overexpressing tumors via positron emission tomography (PET) and single photon emission computed tomography (SPECT) is being notable. On one side, such noninvasive and repetitive monitoring of the activity of EGFR at the kinase level is intended to provide a direct measure of EGFR occupancy and inhibition by EGFR-targeting drugs. On the other side, all oncologic imaging tracers are molecularly targeted radiopharmaceuticals, which are strongly dependent on the tumor biochemistry including increased metabolism, hyperproliferation, angiogenesis, hypoxia, apoptosis, and specific tumor biomarkers (tumor specific antigens and tumor-specific receptors). The present article is an attempt to reconcile these two vital standpoints influencing the choice of appropriate radiolabeled agents for PET and SPECT imaging aimed to support the development of a new generation of multi-targeted kinase inhibitors in the time ahead, because the routine accomplishment of drug selectivity for particular protein kinases is a substantial challenge.
authors.affiliation: Department of Material Science and Chemistry, Faculty of Systems Engineering, Wakayama University, 930 Sakaedani, Wakayama, 640-8510 Japan. petar.mitrasinovic@yahoo.com
authors.forename: Petar M
authors.initials: PM
authors.lastname: Mitrasinovic
mesh_terms: D055088:Early Detection of Cancer / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D049268:Positron-Emission Tomography / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016719:Radioimmunodetection / Q000379:methods; D019275:Radiopharmaceuticals; D015398:Signal Transduction; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D047428:Protein Kinase Inhibitors; D019275:Radiopharmaceuticals; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases