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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
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by
Katrin Tiemann1, Carolina Garri1, Jeffrey Wang1
1Lawrence J. Ellison Institute for Transformative Medicine, Center for Applied Molecular Medicine, University of Southern California.
Abstract:
Cancer patients with an aberrant regulation of the protein phosphorylation networks are often treated with the tyrosine kinase inhibitors. Response rates approaching 85% are common. Unfortunately, patients often become refractory to the treatment by altering their signal transduction pathways. An implementation of the expression profiling with microarrays can identify the overall mRNA-level changes, and proteomics can identify the overall changes in protein levels or can identify the proteins involved, but the activity of the signal transduction pathways can only be established by interrogating post-translational modifications of the proteins. As a result, the ability to identify whether a drug treatment is successful or whether resistance arose, or the ability to characterize any alterations in the signaling pathways, is an important clinical challenge. Here, we provide a detailed explanation of antibody arrays as a tool which can identify system-wide alterations in various post-translational modifications (e.g., phosphorylation). One of the advantages of using antibody arrays includes their accessibility (an array does not require either an expert in proteomics or costly equipment) and speed. The availability of arrays targeting a combination of post-translational modifications is the primary limitation. In addition, unbiased approaches (phosphoproteomics) may be more suitable for the novel discovery, whereas antibody arrays are ideal for the most widely characterized targets.
Insights
Antibody arrays offer a rapid and accessible method to monitor protein post-translational modifications, crucial for understanding cancer drug resistance. This technique helps assess treatment success and signaling pathway alterations in patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Aberrant protein phosphorylation networks are common in cancer, leading to resistance against tyrosine kinase inhibitors.
- Monitoring signal transduction pathway activity is critical for evaluating drug efficacy and resistance mechanisms.
- Current methods like expression profiling and proteomics have limitations in assessing pathway activity via post-translational modifications.
Purpose of the Study:
- To explain antibody arrays as a tool for identifying system-wide alterations in protein post-translational modifications, particularly phosphorylation.
- To highlight the clinical challenge of monitoring drug treatment success and resistance in cancer patients.
- To discuss the advantages and limitations of antibody arrays in this context.
Main Methods:
- Detailed explanation of antibody array technology for interrogating post-translational modifications.
- Comparison with other methods like microarrays and proteomics.
- Discussion of antibody array accessibility, speed, and limitations.
Main Results:
- Antibody arrays can identify system-wide changes in post-translational modifications, such as phosphorylation.
- These arrays are accessible, do not require expert knowledge or costly equipment, and provide rapid results.
- A key limitation is the availability of arrays targeting diverse post-translational modifications.
Conclusions:
- Antibody arrays are a valuable and practical tool for assessing post-translational modifications in clinical settings.
- They aid in understanding cancer drug response and resistance by characterizing signaling pathway alterations.
- While phosphoproteomics is suited for novel discoveries, antibody arrays are ideal for well-characterized targets.
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