The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease

ABSTRACT

Introduction: Chronic graft-versus-host disease (cGVHD) continues to be the leading cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an increasingly applied curative method for both benign and malignant hematologic disorders. Biomarker identification is crucial for the development of noninvasive and cost-effective cGVHD diagnostic, prognostic, and predictive test for use in clinic. Furthermore, biomarkers may help to gain a better insight on ongoing pathophysiological processes. The recent widespread application of omics technologies including genomics, transcriptomics, proteomics and cytomics provided opportunities to discover novel biomarkers.

Areas covered: This review focuses on biomarkers identified through omics that play a critical role in target identification for drug development, and that were verified in at least two independent cohorts. It also summarizes the current status on omics tools used to identify these useful cGVHD targets. We briefly list the biomarkers identified and verified so far. We further address challenges associated to their exploitation and application in the management of cGVHD patients. Finally, insights on biomarkers that are drug targetable and represent potential therapeutic targets are discussed.

Expert commentary: We focus on biomarkers that play an essential role in target identification.

KEYWORDS:

• Chronic graft-versus-host disease (cGVHD)
• allogeneic hematopoietic stem cell transplantation (allo-HSCT)
• biomarkers
• omics
• therapy

Declaration of interest

S Paczesny has a patent on ‘Methods of detection of graft-versus-host disease’ licensed to Viracor-IBT Laboratories. 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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was funded by National Cancer Institute [R01CA 168814, to S.P.], and National Institute of Diabetes and Digestive and Kidney Diseases [T32 DK007519, to D.A.], Leukemia and Lymphoma Scholar Award [grant1293-15, to S.P.], Lilly Physician Scientist Initiative Award (to S.P.).