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711117.pdf (24.98 MB)

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2021

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cc-by (c) Maroni, Giorgia et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/177192

Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer

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Recurs relacionat

https://doi.org/10.1038/s42003-021-01897-6

Resum

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.

Matèries

Càncer de pulmó, Mortalitat

Matèries (anglès)

Lung cancer, Mortality

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

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. Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer. _Communications Biology_. 2021. Vol. 4. [consulta: 7 de maig de 2026]. ISSN: 2399-3642. [Disponible a: https://hdl.handle.net/2445/177192]

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