Identification of accessible human cancer biomarkers using ex vivo chemical proteomic strategies.
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.
Kischel
Philippe
P
Belgian National Fund for Scientific Research, University of Liège, Metastasis Research Laboratory, Center for Experimental Cancer Research, Bât. B23, CHU Sart-Tilman Liège, B-4000 Liège, Belgium. philippe.kischel@ulg.ac.be
Waltregny
David
D
Castronovo
Vincent
V
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000097:blood / Q000737:chemistry*; D001826:Body Fluids / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D010477:Perfusion; D020543:Proteome / Q000737:chemistry; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D008024:Ligands; D020543:Proteome