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Published on: January 22, 2013
Using Reverse Phase Protein Array (RPPA) to Identify and Target Adaptive Resistance
Marilyne Labrie1, Yong Fang2, Nicholas D Kendsersky2
1Knight Cancer Institute, Oregon Health and Sciences University, Portland, OR, USA. labriem@ohsu.edu.
Abstract:
Tumor cells and the tumor ecosystem rapidly evolve in response to therapy. This tumor evolution results in the rapid emergence of drug resistance that limits the magnitude and duration of response to therapy including chemotherapy, targeted therapy, and immunotherapy. Thus, there is an urgent need to understand and interdict tumor evolution to improve patient benefit to therapy. Reverse phase protein array (RPPA) provides a powerful tool to evaluate and develop approaches to target the processes underlying one form of tumor evolution: adaptive evolution. Tumor cells and the tumor microenvironment rapidly evolve through rewiring of protein networks to bypass the effects of therapy. In this review, we present the concepts underlying adaptive resistance and use of RPPA in understanding resistance mechanisms and identification of effective drug combinations. We further demonstrate that this novel information is resulting in biomarker-driven trials aimed at targeting adaptive resistance and improving patient outcomes.
Insights
Tumor cells adapt to therapy by rewiring protein networks, leading to drug resistance. Understanding this adaptive evolution using Reverse Phase Protein Array (RPPA) can reveal new therapeutic strategies and improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Cancer cells and their environment rapidly evolve under therapeutic pressure.
- This evolution leads to acquired drug resistance, limiting treatment efficacy across chemotherapy, targeted therapy, and immunotherapy.
- Understanding and interrupting tumor evolution is critical for enhancing patient response to cancer treatments.
Purpose of the Study:
- To review the concepts of adaptive resistance in tumors.
- To highlight the utility of Reverse Phase Protein Array (RPPA) in dissecting tumor evolution and resistance mechanisms.
- To demonstrate how RPPA-driven insights can inform the development of novel therapeutic strategies and combination therapies.
Main Methods:
- Review of existing literature on tumor adaptive resistance.
- Discussion of Reverse Phase Protein Array (RPPA) as a technology for analyzing protein network alterations.
- Analysis of how RPPA data can identify resistance mechanisms and guide drug combination strategies.
Main Results:
- Adaptive resistance arises from rapid rewiring of protein networks within tumor cells and the microenvironment.
- RPPA is a powerful tool for evaluating these adaptive changes and identifying key nodes in resistance pathways.
- Insights from RPPA can uncover effective drug combinations to overcome adaptive resistance.
Conclusions:
- Targeting adaptive resistance is a crucial strategy to improve patient benefit from cancer therapies.
- RPPA provides valuable data for understanding resistance mechanisms and developing biomarker-driven clinical trials.
- Future research should focus on leveraging RPPA-derived information to design trials that specifically target adaptive resistance, ultimately improving patient outcomes.
