Walter Berger

TL;DR: Cichna et al. as discussed by the authors found that hypomethylation of the ABCC1 promoter is not cancer type-specific but occurs in cancer cell lines of different origins.

TL;DR: In vivo experiments performed with the dichlorido precursor, (Ph2C-Cp)2MoCl2 and the in vitro most active complex, containing the thioflavone ligand, showed an inhibition of tumour growth.

Abstract: Simple Summary Solitary fibrous tumor of the pleura (SFT) is an orphan disease resistant to standard systemic therapy. We managed to establish two patient-derived cell models characterized as SFT by the NAB2-STAT6 gene fusion. Cell lines were tested for drug responsiveness in vitro. Trabectedin and distinct multi-tyrosine kinase inhibitors were effective as single agents. Most interestingly, the combination of trabectedin with ponatinib or dasatinib showed synergistic effects against fusion-positive SFT cell viability, thus suggesting two novel, potentially interesting treatment regimens for this rare and, to date, treatment-refractory disease. Abstract Solitary fibrous tumor of the pleura (SFT) is a rare disease. Besides surgery combined with radiotherapy in nondisseminated stages, curative options are currently absent. Out of fourteen primo-cell cultures, established from surgical SFT specimens, two showed stable in vitro growth. Both cell models harbored the characteristic NAB2-STAT6 fusion and were further investigated by different preclinical methods assessing cell viability, clone formation, and protein regulation upon single-drug treatment or in response to selected treatment combinations. Both fusion-positive cell models showed—in line with the clinical experience and the literature—a low to moderate response to most of the tested cytotoxic and targeted agents. However, the multi-tyrosine kinase inhibitors ponatinib and dasatinib, as well as the anti-sarcoma compound trabectedin, revealed promising activity against SFT growth. Furthermore, both cell models spontaneously presented strong FGFR downstream signaling targetable by ponatinib. Most interestingly, the combination of either ponatinib or dasatinib with trabectedin showed synergistic effects. In conclusion, this study identified novel trabectedin-based treatment combinations with clinically approved tyrosine kinase inhibitors, using two newly established NAB2-STAT6 fusion-positive cell models. These findings can be the basis for anti-SFT drug repurposing approaches in this rare and therapy-refractory disease.