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MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition.
Mollaoglu, Gurkan; Guthrie, Matthew R; Böhm, Stefanie; Brägelmann, Johannes; Can, Ismail; Ballieu, Paul M; Marx, Annika; George, Julie; Heinen, Christine; Chalishazar, Milind D; Cheng, Haixia; Ireland, Abbie S; Denning, Kendall E; Mukhopadhyay, Anandaroop; Vahrenkamp, Jeffery M; Berrett, Kristofer C; Mosbruger, Timothy L; Wang, Jun; Kohan, Jessica L; Salama, Mohamed E; Witt, Benjamin L; Peifer, Martin; Thomas, Roman K; Gertz, Jason; Johnson, Jane E; Gazdar, Adi F; Wechsler-Reya, Robert J; Sos, Martin L; Oliver, Trudy G.
Afiliação
  • Mollaoglu G; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Guthrie MR; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Böhm S; Molecular Pathology, Institute for Pathology, Medical Faculty, University of Cologne, 50937 Cologne, Germany; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
  • Brägelmann J; Molecular Pathology, Institute for Pathology, Medical Faculty, University of Cologne, 50937 Cologne, Germany; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
  • Can I; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Ballieu PM; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Marx A; Molecular Pathology, Institute for Pathology, Medical Faculty, University of Cologne, 50937 Cologne, Germany; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
  • George J; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
  • Heinen C; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
  • Chalishazar MD; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Cheng H; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Ireland AS; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Denning KE; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Mukhopadhyay A; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Vahrenkamp JM; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Berrett KC; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Mosbruger TL; Huntsman Cancer Institute, Bioinformatics Shared Resource, Salt Lake City, UT 84112, USA.
  • Wang J; Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Kohan JL; Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT 84112, USA.
  • Salama ME; Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT 84112, USA.
  • Witt BL; Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT 84112, USA.
  • Peifer M; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
  • Thomas RK; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany; Department of Pathology, University Hospital Cologne, 50937 Cologne, Germany; German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120
  • Gertz J; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
  • Johnson JE; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Gazdar AF; Department of Pathology, Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75235, USA.
  • Wechsler-Reya RJ; Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Sos ML; Molecular Pathology, Institute for Pathology, Medical Faculty, University of Cologne, 50937 Cologne, Germany; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany. Electronic address: martin.sos@uni-koeln.de.
  • Oliver TG; Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA. Electronic address: trudy.oliver@hci.utah.edu.
Cancer Cell ; 31(2): 270-285, 2017 02 13.
Article em En | MEDLINE | ID: mdl-28089889
ABSTRACT
Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low "variant" subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which, combined with chemotherapy, strongly suppresses tumor progression and increases survival. These data identify molecular features for patient stratification and uncover a potential targeted treatment approach for MYC-driven SCLC.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas c-myc / Inibidores de Proteínas Quinases / Carcinoma de Pequenas Células do Pulmão / Aurora Quinases / Neoplasias Pulmonares Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas c-myc / Inibidores de Proteínas Quinases / Carcinoma de Pequenas Células do Pulmão / Aurora Quinases / Neoplasias Pulmonares Idioma: En Ano de publicação: 2017 Tipo de documento: Article