The potential role of the extracellular matrix in the activity of trabectedin in UPS and L-sarcoma: evidences from a patient‐derived ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-05-11

AUTHORS

Alessandro De Vita, Federica Recine, Giacomo Miserocchi, Federica Pieri, Chiara Spadazzi, Claudia Cocchi, Silvia Vanni, Chiara Liverani, Anna Farnedi, Francesco Fabbri, Valentina Fausti, Roberto Casadei, Francesca Brandolini, Giorgio Ercolani, Davide Cavaliere, Alberto Bongiovanni, Nada Riva, Lorena Gurrieri, Giandomenico Di Menna, Sebastiano Calpona, Silvia Angela Debonis, Laura Mercatali, Toni Ibrahim

ABSTRACT

BackgroundSoft tissue sarcomas (STS) are a rare group of solid neoplasm including among others liposarcoma, leiomyosarcoma (L-sarcoma) and undifferentiated pleomorphic sarcoma (UPS) entities. The current first-line treatment is represented by anthracycline based- regimens, second-line may include trabectedin. Currently the activity of trabectedin and its mechanism of action is not completely elucidated.MethodsTaking the advantages of our 3D patient-derived primary culture translational model we performed genomic-, chemobiogram, proteomic- and in vivo analysis in a UPS culture (S1). Furthermore pharmacological profiling of a UPS and L-sarcoma patient-derived case series and in silico analysis were carried out.ResultsTrabectedin exhibited an increased activity in 3D respect to 2D cultures suggesting an extracellular matrix (ECM) and timp1 involvement in its mechanism of action. Moreover 3D S1 xenotranspanted zebrafish model showed an increased sensitivity to trabectedin. Finally the results were further validated in a UPS and L-sarcoma case series.ConclusionsTaken together these results confirmed the activity of trabectedin in these STS histotypes. Moreover the data underline the ECM involvement in the cytotoxic effect mediated by trabectedin and could open the door for researches aimed to focus on the patient setting that could benefit from this agent. More... »

PAGES

165

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13046-021-01963-1

DOI

http://dx.doi.org/10.1186/s13046-021-01963-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1137907446

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33975637


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