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Signaling pathway profiling by reverse-phase protein array for personalized cancer medicine
1Division of Chemotherapy and Clinical Research, Translational Research Group, National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
Deregulation of intracellular signaling through accumulation of genetic alterations is a hallmark of cancer. In the past few decades, concerted and systematic efforts have been made to identify key genetic alterations and to develop therapeutic agents targeting active signaling molecules. However, the efficacy of molecular therapeutics often varies among individuals, and precise mapping of active molecules in individual patients is now considered an essential for therapy optimization. Reverse-phase protein array or microarray (RPPA or RPPM) is an emerging antibody-based highly quantitative proteomic technology, especially suitable for profiling of expression and modification of signaling proteins in low abundance. Because the supply of clinical materials is often limited, RPPA technology is highly advantageous for clinical proteomics in view of its high sensitivity as well as accurate quantification. RPPA has now begun to be incorporated into various clinical trials employing molecular-targeted therapeutics. In this article we review and discuss the application of RPPA technology in the fields of basic, preclinical, and clinical research. The RPPA Global Workshop was recently launched to accelerate the exchange of rapidly expanding knowledge of this fascinating technology among academic laboratories and industries worldwide. This article is part of a Special Issue entitled: Medical Proteomics.
Insights
Reverse-phase protein array (RPPA) technology offers sensitive and quantitative proteomic profiling for cancer research. This method is crucial for optimizing molecular therapies by mapping active signaling molecules in individual patients.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Cancer is characterized by deregulated intracellular signaling due to genetic alterations.
- Identifying key genetic changes and targeting active signaling molecules are crucial for cancer therapy.
- Therapeutic efficacy varies, necessitating precise molecular profiling for personalized treatment.
Purpose of the Study:
- To review and discuss the application of Reverse-Phase Protein Array (RPPA) technology in cancer research.
- To highlight RPPA's advantages in profiling signaling proteins for therapy optimization.
- To discuss RPPA's role in basic, preclinical, and clinical research, including its integration into clinical trials.
Main Methods:
- Reverse-phase protein array (RPPA) technology, an antibody-based quantitative proteomic method.
- Profiling of protein expression and modification, particularly for low-abundance signaling proteins.
- Application in clinical proteomics due to high sensitivity and accurate quantification with limited clinical samples.
Main Results:
- RPPA is highly suitable for profiling signaling proteins, even those present in low abundance.
- The technology provides sensitive and accurate quantification, making it advantageous for clinical proteomics with limited samples.
- RPPA is increasingly incorporated into clinical trials for molecular-targeted therapeutics.
Conclusions:
- RPPA is a valuable tool for molecularly characterizing cancers and optimizing targeted therapies.
- Its sensitivity and quantitative nature make it ideal for clinical proteomics and personalized medicine.
- The RPPA Global Workshop aims to foster knowledge exchange and advance the technology's application worldwide.
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