Enzymatic assays: Biomarkers for drug response prediction using kinases and phosphatases
Protein tyrosine phosphatases (PTPs) and protein tyrosine and serine/threonine kinases (PTKs, STKs) are important regulators of signal transduction pathways in tumour and immune cells, and key targets in precision medicine. Currently, most analytical methods focus on the detection of these crucial enzymes at RNA or protein abundance levels. We developed an innovative method to monitor multiple phosphatase and kinase activities in patient-derived materials like blood and tumour tissues. The target pathways, all controlled by both phosphatases and kinases, include the checkpoint and immune receptors like PD1, CTLA4, LAG3, 4-1BB, CD40, CD20, OX40, TIGIT and GITR. This substrate-specific assay is a valuable, novel tool for biomarker discovery in (immuno-)oncology.
Here we will present a multiplex peptide microarray test and its application in biomarker discovery for tailoring targeted therapies (triple-T approach). It is combined with kinase activity profiling on the same platform. We investigated renal tumour tissues with high and low levels of TILs (tumour-infiltrating lymphocytes) as well as peripheral blood mononuclear cells from melanoma patients treated with checkpoint blockers.
About Dr. Rob Ruijtenbeek
Dr. Rob Ruijtenbeek is Vice President R&D at Pamgene (‘s-Hertogenbosch, The Netherlands), where he heads a multidisciplinary R&D team performing research and development of peptide microarray products and applications in the field of kinases, phosphatases, nuclear receptors and other drug targets. The focus of his current research is the application of peptide microarrays in biomarker discovery in clinical oncology, predicting response to therapy. He is affiliated with the medicinal chemistry and chemical biology group of Utrecht University, where new applications for the peptide microarray technology are investigated in the area of pharmaceutical research & development. This has resulted in multiple scientific publications, patent applications and commercialized products.
Rob Ruijtenbeek holds a M.Sc. degree in both biochemistry and organic chemistry from the University of Nijmegen (1996) and received his Ph.D. degree in 2001 at the faculty of Pharmacy of the University of Utrecht, The Netherlands.