Trabectedin Is Active against Two Novel, Patient-Derived Solitary Fibrous Pleural Tumor Cell Lines and Synergizes with Ponatinib
- Author(s)
- Bahil Ghanim, Dina Baier, Christine Pirker, Leonhard Muellauer, Katharina Sinn, Gyoergy Lang, Konrad Hoetzenecker, Walter Berger
- 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.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Medizinische Universität Wien, Research Cluster Translational Cancer Therapy Research
- Journal
- Cancers
- Volume
- 14
- No. of pages
- 16
- ISSN
- 2072-6694
- DOI
- https://doi.org/10.3390/cancers14225602
- Publication date
- 11-2022
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301904 Cancer research, 301305 Medical chemistry, 302055 Oncology
- Keywords
- ASJC Scopus subject areas
- Oncology, Cancer Research
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/74a71565-dfd3-4334-b10c-b09579ff7380