Proteomic approaches for investigation of therapy resistance in cancer.
Resistance to anticancer therapy is a major obstacle for successful management of patients in oncology. Although in the past, various biological mechanisms involved in therapy resistance, in particular multidrug resistance, have been identified, cancer patients did not really benefit. The mechanisms include the enhanced activity of drug extrusion pumps, modulation of cellular death pathways, alteration and repair of target molecules and various other mechanisms. Together they build a complex network mediating an individual therapy-resistant phenotype. The improved description of this multifactorial network should be useful for prediction of treatment response and would allow to design an individual-tailored therapy regiment. Proteome analyzing technologies appear as powerful tools for identifying new factors and protein expression profiles associated with anticancer therapy resistance. In the last years, the application of proteomic techniques identified multiple new factors or protein expression signatures in drug-resistant cell models and cancerous tissues. However, the functional role and the clinical impact of these findings are not yet clarified. So far, none of the proteomic data were useful for the development of improved diagnostic tests, for prediction of individual therapy response or for development of updated chemosensitizers. Here, the previous therapy resistance-related proteome data and future perspectives will be discussed.
Institute of Pathology, Charité Campus Mitte, Berlin, Germany. hermann.lage@charite.de.
Hermann
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Lage