Identification of accessible human cancer biomarkers using ex vivo chemical proteomic strategies

Abstract

One promising avenue towards the development of more selective, better anticancer drugs lies in the targeted delivery of bioactive compounds to the tumor environment by means of binding molecules specific for tumor-associated biomarkers. Eligibility of such markers for therapeutic ideally use three criteria: accessibility from the bloodstream; expression at sufficient level, and no (or much lower) expression in normal tissues. Most current discovery strategies (such as biomarker searching into body fluids) provide no clue as to whether proteins of interest are accessible, in human tissues, to suitable high-affinity ligands, such as systemically delivered monoclonal antibodies. To address this limitation, our group recently developed two methodologies based on chemical proteomic modifications, enabling the discovery of proteins accessible from the bloodstream and the extracellular space in human pathological tissues. In this review, we will discuss the potential benefits of these methodologies for the fast discovery of therapeutically valuable biomarkers.

Keywords::

• biomarker discovery
• biotinylation
• breast cancer
• tandem mass spectrometry
• tumor targeting

Financial & competing interests disclosure

This work was supported by the EU FP6 framework program STROMA. Grant sponsors of this work include also the National Fund for Scientific Research (Belgium), the Centre Anti-Cancéreux près l’Université de Liège and the Léon Frédéricq foundation. Philippe Kischel is a Research Fellow and David Waltregny is a Senior Research Associate of the Belgian National Fund for Scientific Research.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.

No writing assistance was utilized in the production of this manuscript.