Protein array-based companion diagnostics in precision medicine

ABSTRACT

Introduction

The development of companion diagnostics (CDx) will increase efficacy and cost-benefit markedly, compared to the currently prevailing trial-and-error approach for treatment. Recent improvements in high-throughput protein technology have resulted in large amounts of predictive biomarkers that are potentially useful components of future CDx assays. Current high multiplex protein arrays are suitable for discovery-based approaches, while low-density and more simple arrays are suitable for use in point-of-care facilities.

Area covered

This review discusses the technical platforms available for protein array focused CDx, explains the technical details of the platforms and provide examples of clinical use, ranging from multiplex arrays to low-density clinically applicable arrays. We thereafter highlight recent predictive biomarkers within different disease areas, such as oncology and autoimmune diseases. Lastly, we discuss some of the challenges connected to the implementation of CDx assays as point-of-care tests.

Expert opinion

Recent advances in the field of protein arrays have enabled high-density arrays permitting large biomarker discovery studies, which are beneficial for future CDx assays. The density of protein arrays range from a single protein to proteome-wide arrays, allowing the discovery of protein signatures that may correlate with drug response. Protein arrays will undoubtedly play a key role in future CDx assays.

KEYWORDS:

• Autoimmune diseases
• companion diagnostics
• cdx
• oncology
• point-of-care
• precision medicine
• predictive biomarkers
• protein array

Article highlights

• Multiple protein array platforms are available for companion diagnostics (CDx) assay development in both the biomarker discovery phase and validation.

• Profiling of autoantibodies is one of the strengths of the protein array technology.

• A large variety of effective drugs are available for the treatment of rheumatoid arthritis (RA) but patient responses to the drugs are very heterogeneous; thus, novel CDx assays are in high demand.

• A large number of predictive biomarkers have been identified in several diseases, such as cancer and RA, yet few seem clinically appealing.

• Protein biomarkers within RA are mainly regarding biologic DMARDs, while in oncology it revolves around first-line chemotherapy or the more novel immune checkpoint inhibitors.

• Implementation of multiplex CDx assays for clinical diagnostic use is challenging but possible.

Declaration of interest

JM Blackburn is affiliated with Sengenics Inc. TW Kragstrup is affiliated to iBIOTECH ApS. Malene Møller Jørgensen is one of the inventors of the EV Array. 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.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This review is part of the PROCIT study financed by the Danish Council for Independent Research (grant no. DFF - 7016-00233).