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Title: Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma
Author: Aliagas, Elisabet
Alay, Ania
Martínez Iniesta, María
Hernández Madrigal, Miguel
Cordero, David
Gausachs Romero, Mireia
Pros, Eva
Saigí, Maria
Busacca, Sara
Sharkley, Annabel J.
Dawson, Alan
Palmero, Ramón
Ruffinelli, José C.
Padrones, Susana
Aso, Samantha
Escobar, Ignacio
Ramos, Ricard
Llatjós, Roger
Vidal, August
Dorca, Eduard
Varela, Mar
Sánchez Céspedes, Montse
Fennell, Dean
Muñoz Pinedo, Cristina
Villanueva Garatachea, Alberto
Solé, Xavi
Nadal, Ernest
Keywords: Mesotelioma
Pronòstic mèdic
Proliferació cel·lular
Cell proliferation
Issue Date: 29-Sep-2021
Publisher: Cancer Research UK
Abstract: Background There is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. Methods We aimed to investigate the antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM. Results Based on publicly available transcriptomic data of MPM, patients with CDK4 or CDK6 overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell models evaluated. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest, thereby increasing cell senescence and increased the expression of interferon signalling pathway and tumour antigen presentation process in culture models of MPM. In vivo preclinical studies showed that palbociclib significantly reduced tumour growth and prolonged overall survival using distinct xenograft models of MPM implanted in athymic mice. Conclusions Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM.
Note: Versió postprint del document publicat a:
It is part of: British Journal of Cancer, 2021
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ISSN: 0007-0920
Appears in Collections:Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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