Beschreibung:
<jats:p>Tyrosine kinase (TK) inhibition has been identified as a promising strategy in the treatment of human malignancies and several synthetic inhibitors have been developed. While the selective blockage of specific TKs is highly effective <jats:italic>in vitro</jats:italic>, clinical results have been less impressive. It has been suggested that the simultaneous inhibition of multiple TKs might lead to more favorable therapeutic results <jats:italic>in vivo</jats:italic>. We have therefore performed a systematic analysis of intratumoral TK expression in order to identify potential targets for a simultaneous kinase inhibition. To this end, we have analyzed the protein expression of membrane-associated epidermal growth factor receptor (EGF-R), Her-2/neu, platelet-derived growth factor receptor (PDGF-R), insulin-like growth factor receptor (IGF-R), c-Kit and of cytoplasmatic c-Abl in 500 human tumors of epithelial, stromal and mesenchymal origin by immunohistochemistry, and found a distinct pattern of kinase expression: EGF-R, PDGF-R and c-Abl were expressed in the majority of malignant tumors, whereas c-Kit, Her-2/neu and IGF-R protein expression was considerably less frequent. Overall, the EGF-R protein expression was correlated with PDGF-R, c-Kit and c-Abl immunoreactivity (<jats:italic>P</jats:italic> = 0.003, <jats:italic>P</jats:italic> = 0.001 and <jats:italic>P</jats:italic> < 0.001, respectively). c-Abl was co-expressed with IGF-R and PDGF-R (<jats:italic>P</jats:italic> = 0.003 and <jats:italic>P</jats:italic> < 0.001, respectively). Kinase co-expression was also seen in tumor subgroups and was particularly significant in breast cancer where IGF-R protein was expressed together with PDGF-R and c-Abl (<jats:italic>P</jats:italic> = 0.003 and <jats:italic>P</jats:italic> = 0.004, respectively), and in colon cancer where PDGF-R was correlated with EGF-R (<jats:italic>P</jats:italic> < 0.001). With the exception of Her-2/neu expression and age, intra-tumoral TK expression was not associated with parameters such as grading or histological subtypes. Taken together, we have found a specific pattern of kinase co-expression and have identified several potential targets for a tumor-specific multimodal TK inhibition.</jats:p>