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Front. Oncol. | doi: 10.3389/fonc.2019.00930

Phospho-Protein Arrays as Effective Tools for Screening Possible Targets for Kinase Inhibitors and Their Use in Precision Pediatric Oncology

  • 1Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Czechia
  • 2Department of Pediatric Oncology, University Hospital Brno, Czechia
  • 3Department of Pathology, University Hospital Brno, Czechia

The specific targeting of signal transduction by low-molecular-weight inhibitors or monoclonal antibodies represents a very promising personalized treatment strategy in pediatric oncology. In this study, we present the successful and clinically relevant use of commercially available phospho-protein arrays for analyses of the phosphorylation profiles of a broad spectrum of receptor tyrosine kinases and their downstream signaling proteins in tumor tissue samples. Although these arrays were made for research purposes on human biological samples, they have already been used by several authors to profile various tumor types. Our study performed a systematic analysis of the advantages and pitfalls of the use of this method for personalized clinical medicine. In certain clinical cases and their series, we demonstrated the important aspects of data processing and evaluation, the use of phospho-protein arrays for single sample and serial sample analyses, and the validation of obtained results by immunohistochemistry, as well as the possibilities of this method for the hierarchical clustering of pediatric solid tumors. Our results clearly show that phospho-protein arrays are apparently useful for the clinical consideration of druggable molecular targets within a specific tumor. Thus, their potential validation for diagnostic purposes may substantially improve the personalized approach in the treatment of relapsed or refractory solid tumors.

Keywords: phospho-protein arrays, receptor tyrosin kinases, Signal Transduction, low-molecular-weight inhibitors, Pediatric solid tumors, phosphorylation profiling

Received: 29 Jun 2019; Accepted: 05 Sep 2019.

Copyright: © 2019 Neradil, Kyr, Polaskova, Kren, Macigova, Skoda, Sterba and Veselska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Renata Veselska, Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, 625 00, South Moravia, Czechia, veselska@sci.muni.cz