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

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Authors

NERADIL Jakub KÝR Michal POLÁŠKOVÁ Kristýna KŘEN Leoš MACIGOVÁ Petra ŠKODA Jan ŠTĚRBA Jaroslav VESELSKÁ Renata

Year of publication 2019
Type Article in Periodical
Magazine / Source Frontiers in Oncology
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.frontiersin.org/articles/10.3389/fonc.2019.00930/full
Doi http://dx.doi.org/10.3389/fonc.2019.00930
Keywords low-molecular-weight inhibitors; pediatric solid tumors; phospho-protein arrays; phosphorylation profiling; receptor tyrosin kinases; signal transduction
Description 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.
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