Please use this identifier to cite or link to this item: https://doi.org/10.1038/s42003-021-01897-6
Title: Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer
Authors: Maroni, Giorgia 
Bassal, Mahmoud A 
Krishnan, Indira
Fhu, Chee Wai 
Savova, Virginia
Zilionis, Rapolas
Maymi, Valerie A
Pandell, Nicole
Csizmadia, Eva
Zhang, Junyan
Storti, Barbara
Castano, Julio
Panella, Riccardo
Li, Jia
Gustafson, Corinne E
Fox, Sam
Levy, Rachel D
Meyerovitz, Claire
Tramontozzi, Peter J
Vermilya, Kimberly
De Rienzo, Assunta
Crucitta, Stefania
Basseres, Daniela S
Weetall, Marla
Branstrom, Art
Giorgetti, Alessandra
Ciampi, Raffaele
Del Re, Marzia
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: Science & Technology
Life Sciences & Biomedicine
Biology
Multidisciplinary Sciences
Life Sciences & Biomedicine - Other Topics
Science & Technology - Other Topics
DIFFERENTIAL EXPRESSION ANALYSIS
BMI-1 ONCOPROTEIN
GENE-EXPRESSION
MICROARRAY ANALYSIS
OVEREXPRESSION
PROGRESSION
CARCINOMA
ATLAS
Issue Date: 14-Apr-2021
Publisher: NATURE PORTFOLIO
Citation: Maroni, Giorgia, Bassal, Mahmoud A, Krishnan, Indira, Fhu, Chee Wai, Savova, Virginia, Zilionis, Rapolas, Maymi, Valerie A, Pandell, Nicole, Csizmadia, Eva, Zhang, Junyan, Storti, Barbara, Castano, Julio, Panella, Riccardo, Li, Jia, Gustafson, Corinne E, Fox, Sam, Levy, Rachel D, Meyerovitz, Claire, Tramontozzi, Peter J, Vermilya, Kimberly, De Rienzo, Assunta, Crucitta, Stefania, Basseres, Daniela S, Weetall, Marla, Branstrom, Art, Giorgetti, Alessandra, Ciampi, Raffaele, Del Re, Marzia, 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 (2021-04-14). Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer. COMMUNICATIONS BIOLOGY 4 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/s42003-021-01897-6
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 sequencing in 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.
Source Title: COMMUNICATIONS BIOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/226657
ISSN: 2399-3642
DOI: 10.1038/s42003-021-01897-6
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