title: Mass spectrometry-based proteomics: from cancer biology to protein biomarkers, drug targets, and clinical applications.
abstract: Proteomics is optimally suited to bridge the gap between genomic information on the one hand and biologic functions and disease phenotypes at the other, since it studies the expression and/or post-translational modification (especially phosphorylation) of proteins--the major cellular players bringing about cellular functions--at a global level in biologic specimens. Mass spectrometry technology and (bio)informatic tools have matured to the extent that they can provide high-throughput, comprehensive, and quantitative protein inventories of cells, tissues, and biofluids in clinical samples at low level. In this article, we focus on next-generation proteomics employing nanoliquid chromatography coupled to high-resolution tandem mass spectrometry for in-depth (phospho)protein profiling of tumor tissues and (proximal) biofluids, with a focus on studies employing clinical material. In addition, we highlight emerging proteogenomic approaches for the identification of tumor-specific protein variants, and targeted multiplex mass spectrometry strategies for large-scale biomarker validation. Below we provide a discussion of recent progress, some research highlights, and challenges that remain for clinical translation of proteomic discoveries.
authors.affiliation: From the Department of Medical Oncology, VUmc-Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Connie R
authors.initials: CR
authors.lastname: Jimenez
authors.affiliation: From the Department of Medical Oncology, VUmc-Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D015195:Drug Design; D057166:High-Throughput Screening Assays; D006801:Humans; D013058:Mass Spectrometry; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins