Towards defining biomarkers indicating resistances to targeted therapies |
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| Authors: | Franziska Stehle Kristin SchulzBarbara Seliger |
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| Affiliation: | Martin Luther University Halle-Wittenberg, Institute of Medical Immunology, Magdeburger Str. 2, D-06112 Halle, Saale, Germany |
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| Abstract: | An impressive, but often short objective response was obtained in many tumor patients treated with different targeted therapies, but most of the patients develop resistances against these drugs. So far, a number of distinct mechanisms leading to intrinsic as well as acquired resistances have been identified in tumors of distinct origin. These can arise from genetic alterations, like mutations, truncations, and amplifications or due to deregulated expression of various proteins and signal transduction pathways, but also from cellular heterogeneity within tumors after an initial response. Therefore, biomarkers are urgently needed for cancer prognosis and personalized cancer medicine. The application of “ome”-based technologies including cancer (epi)genomics, next generation sequencing, cDNA microarrays and proteomics might led to the predictive or prognostic stratification of patients to categorize resistance mechanisms and to postulate combinations of treatment strategies. This review discusses the implementation of proteome-based analysis to identify markers of pathway (in)activation in tumors and the resistance mechanisms, which represent major clinical problems as a tool to optimize individually tailored therapies based on targeted drugs. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. |
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| Keywords: | 2 DE, 2-dimensional electrophoresis ABPP, activity-based protein profiling BFGF, basic fibroblast growth factor CML, chronic myeloid leukemia CRC, colorectal cancer DIGE, differential in gel electrophoresis EGF(R), epidermal growth factor (receptor) EMT, epithelial to mesenchymal transition FGF 2, fibroblast growth factor-2 FT-ICR MS, Fourier transform ion cyclotron mass spectrometry HGFR, hepatocyte growth factor receptor ICAT, isotope-coded affinity tags iTRAQ, isobaric tags for relative and absolute quantification JAK, janus kinase KRAB, Krueppl-associated box LC, liquid chromatography mAbs, monoclonal antibody miRNA, micro-RNA mTOR, mammalian target of rapamycin NSCLC, non-small-cell lung cancer PFS, progression free survival PI3K, phosphatidylinositol 3 kinase PTEN, phosphatase and tensin homologue PTM, post-translational modifications RCC, renal cell carcinoma RTK, receptor tyrosine kinase SELDI-TOF MS, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry SILAC, stable isotypelabeling by amino acids in cell culture TKI, tyrosine kinase inhibitor VEGF(R), the vascular endothelial growth factor (receptor) WT, wild type ZNF, zink finger |
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