Epithelioid sarcoma (ES) is a rare disease representing <1% of soft tissue sarcomas. Current therapies are based on anthracycline alone or in combination with ifosfamide or other cytotoxic drugs. ES is still characterized by a poor prognosis with high rates of recurrence. Indeed, for years, ES survival rates have remained stagnant, suggesting that conventional treatments should be revised and improved. New therapeutic approaches are focused to target the key regulators of signaling pathways, the causative markers of tumor pathophysiology. To this end, we selected, among the drugs to which an ES cell line is highly sensitive, those that target signaling pathways known to be dysregulated in ES. In particular, we found a key role for GSK‐3β, which results in upregulation in tumor versus normal tissue samples and associated to poor prognosis in sarcoma patients. Following this evidence, we evaluated CHIR99021, a GSK‐3 inhibitor, as a potential drug for use in ES therapy. Our data highlight that, in ES cells, CHIR99021 induces cell cycle arrest, mitotic catastrophe (MC) and autophagic response, resulting in reduced cell proliferation. Our results support the potential efficacy of CHIR99021 in ES treatment and encourage further preclinical and clinical studies.

Russi, S., Sgambato, A., Bochicchio, A. M., Zoppoli, P., Aieta, M., Capobianco, A. M. L., Ruggieri, V., Zifarone, E., Falco, G., Laurino, S., Chir99021, trough gsk‐3β targeting, reduces epithelioid sarcoma cell proliferation by activating mitotic catastrophe and autophagy, <<INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES>>, 2021; 22 (20): 11147-N/A. [doi:10.3390/ijms222011147] [http://hdl.handle.net/10807/205245]

Chir99021, trough gsk‐3β targeting, reduces epithelioid sarcoma cell proliferation by activating mitotic catastrophe and autophagy

Sgambato, A.;Ruggieri, V.;Falco, G.;Laurino, S.
2021

Abstract

Epithelioid sarcoma (ES) is a rare disease representing <1% of soft tissue sarcomas. Current therapies are based on anthracycline alone or in combination with ifosfamide or other cytotoxic drugs. ES is still characterized by a poor prognosis with high rates of recurrence. Indeed, for years, ES survival rates have remained stagnant, suggesting that conventional treatments should be revised and improved. New therapeutic approaches are focused to target the key regulators of signaling pathways, the causative markers of tumor pathophysiology. To this end, we selected, among the drugs to which an ES cell line is highly sensitive, those that target signaling pathways known to be dysregulated in ES. In particular, we found a key role for GSK‐3β, which results in upregulation in tumor versus normal tissue samples and associated to poor prognosis in sarcoma patients. Following this evidence, we evaluated CHIR99021, a GSK‐3 inhibitor, as a potential drug for use in ES therapy. Our data highlight that, in ES cells, CHIR99021 induces cell cycle arrest, mitotic catastrophe (MC) and autophagic response, resulting in reduced cell proliferation. Our results support the potential efficacy of CHIR99021 in ES treatment and encourage further preclinical and clinical studies.
2021
Inglese
Russi, S., Sgambato, A., Bochicchio, A. M., Zoppoli, P., Aieta, M., Capobianco, A. M. L., Ruggieri, V., Zifarone, E., Falco, G., Laurino, S., Chir99021, trough gsk‐3β targeting, reduces epithelioid sarcoma cell proliferation by activating mitotic catastrophe and autophagy, <<INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES>>, 2021; 22 (20): 11147-N/A. [doi:10.3390/ijms222011147] [http://hdl.handle.net/10807/205245]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/205245
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 12
social impact