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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
Investigation of cancer drug resistance mechanisms by phosphoproteomics
Joelle C Boulos1, Muhammad Rahama Yousof Idres1, Thomas Efferth1
1Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomolecular Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Abstract:
Cancer cell mutations can be identified by genomic and transcriptomic techniques. However, they are not sufficient to understand the full complexity of cancer heterogeneity. Analyses of proteins expressed in cancers and their modification profiles show how these mutations could be translated at the functional level. Protein phosphorylation is a major post-translational modification critical for regulating several cellular functions. The covalent addition of phosphate groups to serine, threonine, and tyrosine is catalyzed by protein kinases. Over the past years, kinases were strongly associated with cancer, thus inhibition of protein kinases emanated as novel cancer treatment. However, cancers frequently develop drug resistance. Therefore, a better understanding of drug effects on tumors is urgently needed. In this perspective, phosphoproteomics arose as advanced tool to monitor cancer therapies and to discover novel drugs. This review highlights the role of phosphoproteomics in predicting sensitivity or resistance of cancers towards tyrosine kinase inhibitors and cytotoxic drugs. It also shows the importance of phosphoproteomics in identifying biomarkers that could be applied in clinical diagnostics to predict responses to drugs.
Insights
Phosphoproteomics analyzes protein phosphorylation to reveal cancer drug responses. This method helps predict cancer treatment sensitivity or resistance, aiding in developing new therapies and diagnostics.
Area of Science:
- Oncology
- Biochemistry
- Proteomics
Background:
- Genomic and transcriptomic methods alone are insufficient for understanding cancer heterogeneity.
- Protein expression and modification analyses are crucial for understanding functional impacts of mutations.
- Protein kinases are key regulators of cellular functions and are implicated in cancer development and drug resistance.
Purpose of the Study:
- To highlight the role of phosphoproteomics in cancer research.
- To review phosphoproteomics' utility in predicting cancer therapy outcomes.
- To explore phosphoproteomics for identifying diagnostic biomarkers.
Main Methods:
- Review of current literature on phosphoproteomics in cancer.
- Analysis of protein phosphorylation patterns.
- Correlation of phosphoproteomic data with drug sensitivity and resistance.
Main Results:
- Phosphoproteomics provides functional insights beyond genomic data.
- This technique can predict cancer sensitivity or resistance to tyrosine kinase inhibitors and cytotoxic drugs.
- Phosphoproteomics aids in identifying potential biomarkers for clinical diagnostics.
Conclusions:
- Phosphoproteomics is an advanced tool for monitoring cancer therapies and discovering novel drugs.
- Understanding protein phosphorylation is vital for overcoming cancer drug resistance.
- Phosphoproteomics holds significant potential for personalized cancer treatment and diagnostics.
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