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Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.
Maynard, Ashley; McCoach, Caroline E; Rotow, Julia K; Harris, Lincoln; Haderk, Franziska; Kerr, D Lucas; Yu, Elizabeth A; Schenk, Erin L; Tan, Weilun; Zee, Alexander; Tan, Michelle; Gui, Philippe; Lea, Tasha; Wu, Wei; Urisman, Anatoly; Jones, Kirk; Sit, Rene; Kolli, Pallav K; Seeley, Eric; Gesthalter, Yaron; Le, Daniel D; Yamauchi, Kevin A; Naeger, David M; Bandyopadhyay, Sourav; Shah, Khyati; Cech, Lauren; Thomas, Nicholas J; Gupta, Anshal; Gonzalez, Mayra; Do, Hien; Tan, Lisa; Bacaltos, Bianca; Gomez-Sjoberg, Rafael; Gubens, Matthew; Jahan, Thierry; Kratz, Johannes R; Jablons, David; Neff, Norma; Doebele, Robert C; Weissman, Jonathan; Blakely, Collin M; Darmanis, Spyros; Bivona, Trever G.
Afiliação
  • Maynard A; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • McCoach CE; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Rotow JK; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Harris L; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Haderk F; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Fran
  • Kerr DL; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Yu EA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Schenk EL; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Tan W; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Zee A; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Tan M; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Gui P; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Lea T; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Wu W; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Urisman A; Department of Pathology University of California, San Francisco, San Francisco, CA 94143, USA.
  • Jones K; Department of Pathology University of California, San Francisco, San Francisco, CA 94143, USA.
  • Sit R; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Kolli PK; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143 USA.
  • Seeley E; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Gesthalter Y; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Le DD; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Yamauchi KA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Naeger DM; Denver Health Medical Center, Denver, CO 80204, USA; Department of Radiology, University of Colorado, Aurora, CO 80045, USA.
  • Bandyopadhyay S; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Shah K; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Cech L; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Thomas NJ; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Gupta A; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Gonzalez M; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Do H; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Tan L; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Bacaltos B; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Gomez-Sjoberg R; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Gubens M; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Jahan T; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kratz JR; Department of Surgery, University of California, San Francisco, CA 94143, USA.
  • Jablons D; Department of Surgery, University of California, San Francisco, CA 94143, USA.
  • Neff N; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Doebele RC; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Weissman J; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
  • Blakely CM; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: collin.blakely@ucsf.edu.
  • Darmanis S; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: spyros.darmanis@czbiohub.org.
  • Bivona TG; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Fran
Cell ; 182(5): 1232-1251.e22, 2020 09 03.
Article em En | MEDLINE | ID: mdl-32822576
ABSTRACT
Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pulmonares Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pulmonares Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article