title: Targeting breast cancer-associated fibroblasts to improve anti-cancer therapy.
abstract: In recent years, mass spectrometry-based proteomics has undergone significant development steps which may be divided into an exploratory phase, a consolidation phase and an application phase. We are in a stage now where we are able to apply mass spectrometric technologies to answer complex and clinically relevant questions. This is demonstrated here with respect to a current hot topic, namely the consideration of the cancer-supporting microenvironment as a target of new and more efficient anti-cancer therapy. Actually, the relevance of micro environmental stromal cells to tumor initiation and promotion has been clearly recognized. However, the individual kind and degree of stroma-derived tumor promotion can so far hardly be determined in patients, and hardly any therapeutic option exists to dismantle the cancer cells of the stroma-derived support. Quite remarkably, the response of stromal cells to standard chemotherapeutics is also rather unknown. In this Perspective, experimental strategies how to address such issues are outlined in detail. Different cell systems are presented as powerful models which allow identifying relevant marker molecules. Targeted proteomics is presented as method of choice for both, drug screening in vitro as well as monitoring drug responses in patients. By this means, a way of classifying different functional tumor promoting mechanisms, evaluating how current treatment strategies may affect cancer-associated fibroblasts, identifying effective drugs targeting these cancer-associated cells and, may be most importantly, demonstrating how combined therapeutic strategies may improve the efficiency of anti-cancer treatments are indicated.
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Austria.
authors.forename: Astrid
authors.initials: A
authors.lastname: Slany
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bileck
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Austria.
authors.forename: Besnik
authors.initials: B
authors.lastname: Muqaku
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Austria. Electronic address: christopher.gerner@univie.ac.at.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D040901:Proteomics; D012107:Research Design; D059016:Tumor Microenvironment / Q000187:drug effects*
keywords: Breast cancer; Cancer-associated fibroblasts; Drug evaluation; Mass spectrometry; Proteome profiling; Targeted proteomics