Signaling pathway profiling using reverse-phase protein array and its clinical applications

ABSTRACT

Introduction: Increased accessibility to next-generation sequencing within the last decade has led to a paradigm shift in cancer treatment from one-size-fits-all medicine to precision medicine providing therapeutic strategies tailored to the requirements of individual patients. However, the effect of even the most successful agent yet tested is only transient, and durable efficacy has yet to be achieved. Genome- and transcriptome-based approaches cannot fully predict the diversity of protein expression patterns or post-translational modifications that directly contribute to cancer pathogenesis and physiology. This underscores the need for concordant proteomic analysis in the next stage of precision medicine.

Areas covered: This review begins with an overview of the recent advances and trends in precision medicine that currently rely on genomics, and highlights the utility of antibody-based reverse-phase protein array (RPPA) technology as a proteomic tool in this context.

Expert commentary: RPPA is well suited for pharmacodynamics analysis in view of its ability to precisely map signaling status using limited amounts of clinical samples. In addition, the cost-effectiveness and rapid turn-around time of the RPPA platform offer a substantial advantage over existing molecular profiling technologies in clinical settings.

KEYWORDS:

• Reverse-phase protein array (RPPA)
• precision medicine
• biomarker panel
• patient stratification
• molecular targeting agents
• signal pathway profiling
• protein phosphorylation

Declaration of interest

T. Yamada received a research grant from Carna BioSciences, Inc. (Kobe Japan). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This study was supported by the National Cancer Center Research and Development Fund (26-A-13 and 26-A-5 to T. Y.), the Acceleration Transformative Research for Medical Innovation (ACT-MS) program of the Japan Agency for Medical Research and Development (AMED) (16im0210804h0001 to T. Y.), and KAKENHI Grants-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (JSPS) (16K14627 and 17H03603 to M. M.).