Advancing translation of biomarkers into regulatory science.

Abstract

Many identified biomarkers have yet to be translated into regulatory science The first biomarker successfully translated into regulatory decision-making at the US FDA was HER2. In 1998, the FDA approved Herceptin (trastuzumab) for treatment of breast cancer patients whose HER2 is overexpressed. Since then, translation of biomarkers into FDA regulatory decision-making has been accelerated and led to an ever increasing number of targeted therapies using biomarkers being approved, as evidenced by the fact that eight drugs (Beleodaq, Blincyto, Cardelga, Harvoni, Lynparza, Viekira Pak, Vimizim and Zykadia) for targeted therapies were approved in 2014. There are many efforts and programs at the FDA which aim to advance the translation of biomarkers into regulatory science [1–3]. Academic institutes and industry have huge investments in biomarker development. In addition, emerging technologies have been used in the discovery of biomarkers [4]. A large number of biomarkers for diagnosis and prognosis, treatment selection and dose on demand have been identified, providing more impetus for translation of biomarkers into regulatory science. Though some biomarkers have been used in the FDA’s regulatory science work, many more identified biomarkers have not yet been translated into regulatory decision-making. The motivation behind this issue of Biomarkers in Medicine is to provide a contemporary summary of advances in translation of biomarkers into regulatory science. MicroRNAs as noninvasive biomarkers have tremendous potential to be translated into regulatory science MicroRNAs (abbreviated as miRNAs) are endogenous small noncoding RNAs that play regulatory roles in gene expression. Expression of some miRNAs has been found to be associated with certain diseases and drug treatment responses. Recent advances in emerging technologies, such as nextgeneration sequencing (NGS) technologies for measuring expression of known miRNAs and discovery of new miRNAs, have identified many miRNAs as biomarkers for diagnosis, prognosis and safety evaluation [5]. Efforts continue unabated with the aim of translating new miRNA biomarkers into regulatory science. Accordingly, this issue solicited expert reviews to shed light on recent biomarker research and to foster translation of miRNA biomarkers into regulatory science. Drug safety is a major factor in regulation and development. This issue collected expert reviews which summarize recent efforts in the application of miRNAs as drug safety biomarkers for hepatotoxicity and cardiotoxicity testing [6–8]. Some miRNAs, such as miR-34a, miR-93–5p, miR-21 and miR-155, have demonstrated potential as biomarkers of nephrotoxicity [7,8]. Translation of miRNAs into drug safety biomarkers in regulatory science has been impeded due to concerns regarding variations among assay methods used to quantify miRNAs and lack of standards [8]. Future efforts to translate miRNA biomarkers into regulatory science for Advancing translation of biomarkers into regulatory science