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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Liposarcoma | Research

The potential role of the extracellular matrix in the activity of trabectedin in UPS and L-sarcoma: evidences from a patient‐derived primary culture case series in tridimensional and zebrafish models

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

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Soft 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.

Methods

Taking 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.

Results

Trabectedin 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.

Conclusions

Taken 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.

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Title: The potential role of the extracellular matrix in the activity of trabectedin in UPS and L-sarcoma: evidences from a patient‐derived primary culture case series in tridimensional and zebrafish models
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
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Liposarcoma
Soft Tissue Sarcoma
Sarcoma
Anthracycline
Lenvatinib
Cytostatic Therapy
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-01963-1

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