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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Phospho-Protein Arrays as Effective Tools for Screening Possible Targets for Kinase Inhibitors and Their Use in
Jakub Neradil1,2, Michal Kyr2, Kristyna Polaskova2
1Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia.
Abstract:
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.
Insights
Phospho-protein arrays offer a promising approach for personalized pediatric cancer treatment by analyzing tumor signaling pathways. This method helps identify druggable targets, potentially improving outcomes for relapsed or refractory solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Personalized Medicine
Background:
- Targeting signal transduction pathways is a key strategy in pediatric oncology.
- Low-molecular-weight inhibitors and monoclonal antibodies are promising therapeutic agents.
- Personalized treatment requires detailed molecular profiling of tumors.
Purpose of the Study:
- To evaluate the clinical utility of phospho-protein arrays for analyzing tumor signaling in pediatric oncology.
- To systematically assess the advantages and limitations of phospho-protein arrays in personalized medicine.
- To demonstrate the application of phospho-protein arrays for identifying druggable targets in pediatric solid tumors.
Main Methods:
- Utilized commercially available phospho-protein arrays to analyze phosphorylation profiles of receptor tyrosine kinases and downstream signaling proteins.
- Performed systematic analysis of data processing, evaluation, and validation using immunohistochemistry.
- Applied phospho-protein arrays for single and serial sample analyses and hierarchical clustering of pediatric solid tumors.
Main Results:
- Demonstrated successful and clinically relevant use of phospho-protein arrays for profiling tumor tissue samples.
- Identified key aspects of data processing, evaluation, and validation for clinical application.
- Showcased the potential for hierarchical clustering of pediatric solid tumors based on phosphorylation profiles.
Conclusions:
- Phospho-protein arrays are valuable tools for identifying druggable molecular targets in specific tumors.
- Validation of phospho-protein arrays for diagnostic purposes can significantly enhance personalized treatment for relapsed or refractory pediatric solid tumors.
- This approach holds potential to improve therapeutic strategies in pediatric oncology.
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02:54Protein Kinases and Phosphatases