Abstract | BACKGROUND: METHODS: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation. RESULTS: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro. CONCLUSION: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.
|
Authors | Dario P Anobile, Paolo Bironzo, Francesca Picca, Marcello F Lingua, Deborah Morena, Luisella Righi, Francesca Napoli, Mauro G Papotti, Alessandra Pittaro, Federica Di Nicolantonio, Chiara Gigliotti, Federico Bussolino, Valentina Comunanza, Francesco Guerrera, Alberto Sandri, Francesco Leo, Roberta Libener, Pablo Aviles, Silvia Novello, Riccardo Taulli, Giorgio V Scagliotti, Chiara Riganti |
Journal | Cancers
(Cancers (Basel))
Vol. 13
Issue 10
(May 12 2021)
ISSN: 2072-6694 [Print] Switzerland |
PMID | 34066159
(Publication Type: Journal Article)
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|