Abstract
Simple SummaryMolecular complexes, such as those comprised of ligands such as hormones binding to their target receptors, are key determinants of health and disease. While research has focused on measuring receptors or ligands independently as biomarkers, very little attention has been given to measuring ligand-receptor complexes, in part, due to the limited availability of suitable technologies to do such measurements. This has led to underappreciation of ligand-receptor complexes as biomarkers in disease, including in cancer. In this commentary, the potential role of ligand-receptor complexes and their importance as biomarkers in cancer is discussed. We also describe a novel RNA aptamer-based technology, designated as ligand-receptor complex-binding aptamers (LIRECAP), that can provide precise measurement of the ligand occupancy of receptors and has potential use as a biomarker discovery platform.Molecular complexes, such as ligand–receptor complexes, are vital for both health and disease and can be shed into the circulation in soluble form. Relatively little is known about the biology of soluble ligand–receptor complexes. The functional importance of such complexes and their potential use as clinical biomarkers in diagnosis and therapy remains underappreciated. Most traditional technologies used to study ligand–receptor complexes measure the individual levels of soluble ligands or receptors rather than the complexes themselves. The fraction of receptors occupied by ligand, and the potential clinical relevance of such information, has been largely overlooked. Here, we review the biological significance of soluble ligand–receptor complexes with a specific focus on their potential as biomarkers of cancer and other inflammatory diseases. In addition, we discuss a novel RNA aptamer-based technology, designated ligand–receptor complex-binding aptamers (LIRECAP), that can provide precise measurement of the fraction of a soluble receptor occupied by its ligand. The potential applicability of the LIRECAP technology as a biomarker discovery platform is also described.
Highlights
The central role of molecular complexes in biology has been well documented
Assays geared towards quantifying ligand–receptor complexes, such as FRET, are generally difficult to apply in a high-throughput platform like that required for analysis of a large numbers of samples or clinical diagnosis [1,17,18,19,20,21,22,23]
We describe a novel RNA aptamer-based biomarker platform, designated for ligand–receptor complex-binding aptamers (LIRECAP), designed to measure fractional occupancy of receptor by ligand and the potential of this platform in cancer research and clinical management
Summary
The central role of molecular complexes in biology has been well documented. Multimolecular complexes, including those formed by ligand–receptor interactions and multimeric receptor interactions, play a significant role in homeostasis; response to infection; and the pathogenesis of a variety of diseases, including cancer, by regulating cell growth and differentiation. Molecular complexes play a important role in regulating immunity. Cancers 2020, 12, 2956 complexes [1,2,3,4,5,6,7,8]. Much therapeutic research is focused on altering ligand–receptor complexes, and on evaluating ligands or receptors individually as biomarkers. Relatively little effort has been directed towards the measurement of the molecular complexes themselves for use as biomarkers of disease or for therapy. Traditional assays have limitations when being applied to quantify such complexes (Table 1)
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