PUBLICATION
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
- De Vita, A., Recine, F., Miserocchi, G., Pieri, F., Spadazzi, C., Cocchi, C., Vanni, S., Liverani, C., Farnedi, A., Fabbri, F., Fausti, V., Casadei, R., Brandolini, F., Ercolani, G., Cavaliere, D., Bongiovanni, A., Riva, N., Gurrieri, L., Di Menna, G., Calpona, S., Debonis, S.A., Mercatali, L., Ibrahim, T.
- ID
- ZDB-PUB-210513-2
- Date
- 2021
- Source
- Journal of experimental & clinical cancer research : CR 40: 165 (Journal)
- Registered Authors
- Keywords
- 3D scaffold, Chemotherapy, Extracellular matrix, Patient‐derived primary cultures, Trabectedin, Undifferentiated pleomorphic sarcoma and L-sarcoma
- MeSH Terms
-
- Humans
- Animals
- Zebrafish
- Antineoplastic Agents, Alkylating/pharmacology*
- Extracellular Matrix
- Sarcoma/drug therapy*
- Trabectedin/pharmacology*
- Disease Models, Animal
- PubMed
- 33975637 Full text @ J. Exp. Clin. Cancer Res.
Citation
De Vita, A., Recine, F., Miserocchi, G., Pieri, F., Spadazzi, C., Cocchi, C., Vanni, S., Liverani, C., Farnedi, A., Fabbri, F., Fausti, V., Casadei, R., Brandolini, F., Ercolani, G., Cavaliere, D., Bongiovanni, A., Riva, N., Gurrieri, L., Di Menna, G., Calpona, S., Debonis, S.A., Mercatali, L., Ibrahim, T. (2021) 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. Journal of experimental & clinical cancer research : CR. 40:165.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping