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http://hdl.handle.net/2445/177192
Title: | Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer |
Author: | Maroni, Giorgia Bassal, Mahmoud A. Krishnan, Indira Chee, Chee Wai Savova, Virginia Zilionis, Rapolas Maymi, Valerie A. Pandell, Nicole Csizmadia, Eva Zhang, Junyan Storti, Barbara Castaño, Julio Panella, Riccardo Li, Jia Gustafson, Corinne E. Fox, Sam Levy, Rachel D. Meyerovitz, Claire V. Tramontozzi, Peter J. Vermilya, Kimberly Rienzo, Assunta De Crucitta, Stefania Bassères, Daniela S. Weetall, Marla Branstrom, Art Giorgetti, Alessandra Ciampi, Raffaele Re, Marzia Del Danesi, Romano Bizzarri, Ranieri Yang, Henry Kocher, Olivier Klein, Allon M. Welner, Robert S. Bueno, Raphael Magli, Maria Cristina Clohessy, John G. Ali, Azhar Tenen, Daniel G. Levantini, Elena |
Keywords: | Càncer de pulmó Mortalitat Lung cancer Mortality |
Issue Date: | 2021 |
Publisher: | Nature Publishing Group |
Abstract: | Lung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencingin aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer. We previously reported a key role for the oncogene BMI-1 in adenocarcinomas. We therefore investigated the effects of in vivo PTC596 treatment, which affects BMI-1 activity, in our murine model. Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s42003-021-01897-6 |
It is part of: | Communications Biology, 2021, vol. 4 |
URI: | http://hdl.handle.net/2445/177192 |
Related resource: | https://doi.org/10.1038/s42003-021-01897-6 |
ISSN: | 2399-3642 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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