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Characterization of anticancer drug resistance by reverse-phase protein array: new targets and strategies
Ann M Cathcart1,2, Hannah Smith1, Marilyne Labrie1,3
1Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Introduction:
Drug resistance is the main barrier to achieving cancer cures with medical therapy. Cancer drug resistance occurs, in part, due to adaptation of the tumor and microenvironment to therapeutic stress at a proteomic level. Reverse-phase protein arrays (RPPA) are well suited to proteomic analysis of drug resistance due to high sample throughput, sensitive detection of phosphoproteins, and validation for a large number of critical cellular pathways.
Areas Covered:
This review summarizes contributions of RPPA to understanding and combating drug resistance. In particular, contributions of RPPA to understanding resistance to PARP inhibitors, BRAF inhibitors, immune checkpoint inhibitors, and breast cancer investigational therapies are discussed. Articles reviewed were identified by MEDLINE, Scopus, and Cochrane search for keywords 'proteomics,' 'reverse-phase protein array,' 'drug resistance,' 'PARP inhibitor,' 'BRAF inhibitor,' 'immune checkpoint inhibitor,' and 'I-SPY' spanning October 1, 1960 - October 1, 2021.
Expert Opinion:
Precision oncology has thus far failed to convert the armament of targeted therapies into durable responses for most patients, highlighting that genetic sequencing alone is insufficient to guide therapy selection and overcome drug resistance. Combined genomic and proteomic analyses paired with creative drug combinations and dosing strategies hold promise for maturing precision oncology into an era of improved patient outcomes.
Insights
Reverse-phase protein arrays (RPPA) help understand cancer drug resistance by analyzing proteomic changes. This proteomic approach is key to improving precision oncology and patient outcomes.
Area of Science:
- Oncology
- Proteomics
- Cancer Biology
Background:
- Drug resistance remains a significant obstacle in cancer therapy.
- Tumor adaptation at the proteomic level contributes to therapeutic resistance.
- Precision oncology requires more than genetic sequencing to overcome resistance.
Purpose of the Study:
- To review the role of Reverse-Phase Protein Arrays (RPPA) in understanding and overcoming cancer drug resistance.
- To highlight RPPA's contributions to studying resistance mechanisms against various targeted therapies.
- To discuss the integration of proteomic data for advancing precision oncology.
Main Methods:
- Literature review of studies utilizing RPPA for cancer drug resistance research.
- Analysis of RPPA applications in resistance to PARP inhibitors, BRAF inhibitors, and immune checkpoint inhibitors.
- Inclusion of data from breast cancer investigational therapies and I-SPY trials.
Main Results:
- RPPA enables high-throughput proteomic analysis, crucial for understanding resistance.
- RPPA effectively detects phosphoproteins and validates key cellular pathways involved in drug resistance.
- The review details RPPA's specific contributions to understanding resistance to several targeted therapies.
Conclusions:
- RPPA is a powerful tool for proteomic analysis in cancer drug resistance research.
- Combined genomic and proteomic analyses are essential for advancing precision oncology.
- Integrating RPPA data can lead to improved therapeutic strategies and patient outcomes.
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