A novel precision medicine approach to treat advanced liposarcoma
Liposarcomas (LPSs) are heterogenous group of soft-tissue sarcomas, which outcome depends strongly on the site of the primary tumor and tumor histotype. At the moment, there are not available any efficacious targeted therapies to treat advanced LPSs. We have discovered recently several new LPS-specific oncogenes, which could serve as a diagnostic biomarkers or precision medicine targets in distinct LPS subtypes. In the present study, we will investigate a role of phosphodiesterase 3A (PDE3A) as a therapy target for anagrelide, and drug combinations, which could show synergy with anagrelide treatment. In addition, we will study prognostic biomarkers, which could predict efficacy of the investigated therapeutics. We will exploit rare LPS cell lines and several state-of-art techniques such as a high-throughput drug screening, kinome and transcriptome analyses to find out answers to our research questions. In addition, possible prognostic biomarkers for the therapy will be investigated by using a large LPS patient samples series. The study will identify an efficacy of anagrelide and the most potent synergistic drug combinations in LPS. Based on the results, an in vivo efficacy of the most promising drugs will be investigated in sequel studies.