Targeted therapy of soft tissue sarcomas |
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Authors: | Wardelmann Eva Chemnitz Jens M Wendtner Clemens-Martin |
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Affiliation: | Institute of Pathology, University Hospital Cologne, Cologne, Germany. |
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Abstract: | Soft tissue sarcomas (STS) are rare mesenchymal cancers with a heterogeneous histology. In terms of oncogenesis, sarcomas may be differentiated into diseases with defined molecular events and sarcomas presenting with complex karyotypes lacking identifiable specific genetic changes or expression profile signatures. The former subtype is amenable to therapy with targeted drugs, especially if the tumor carries a consistent causal mutation occurring early in the disease development. While targeted therapy based on tyrosine kinase inhibition such as imatinib and second generation tyrosine kinase inhibitors plays an important role in the treatment of gastrointestinal stromal tumors (GIST), some progress was also achieved in non-GIST sarcomas. Targeting the PI3 kinase/Akt pathway has been shown to be clinically promising in a diversity of different sarcoma subtypes, and inhibition of the vascular endothelial growth factor (VEGF)/VEGF receptor pathway is of special interest in vascular sarcoma subtypes. MDM2 and p53 seem to be interesting targets for STS, but their role has yet to be defined in further clinical trials. Modification of epigenetic mechanisms, especially deacetylation, might be crucial in other STS subtypes such as translocation-associated entities, but its role has yet to be clinically confirmed. Inclusion of patients in controlled clinical trials combined with a translational research platform is critical for further progress. |
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