Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/180823
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, Montserrat Fennell, Dean Muñoz Pinedo, Cristina Villanueva Garatachea, Alberto Solé, Xavi Nadal, Ernest |
Keywords: | Mesotelioma Immunoteràpia Pronòstic mèdic Proliferació cel·lular Mesothelioma Immunotheraphy Prognosis 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: https://doi.org/10.1038/s41416-021-01547-y |
It is part of: | British Journal of Cancer, 2021 |
URI: | http://hdl.handle.net/2445/180823 |
Related resource: | https://doi.org/10.1038/s41416-021-01547-y |
ISSN: | 0007-0920 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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