Mollaoglu, Gurkan ORCID: 0000-0003-0679-7463, Guthrie, Matthew R., Boehm, Stefanie, Braegelmann, 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 ORCID: 0000-0002-5243-5503, Thomas, Roman K., Gertz, Jason ORCID: 0000-0001-7568-6789, Johnson, Jane E., Gazdar, Adi F., Wechsler-Reya, Robert J., Sos, Martin L. and Oliver, Trudy G. (2017). MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition. Cancer Cell, 31 (2). S. 270 - 286. CAMBRIDGE: CELL PRESS. ISSN 1878-3686

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Mollaoglu, GurkanUNSPECIFIEDorcid.org/0000-0003-0679-7463UNSPECIFIED
Guthrie, Matthew R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boehm, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braegelmann, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Can, IsmailUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ballieu, Paul M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marx, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinen, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chalishazar, Milind D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cheng, HaixiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ireland, Abbie S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denning, Kendall E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mukhopadhyay, AnandaroopUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vahrenkamp, Jeffery M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berrett, Kristofer C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mosbruger, Timothy L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohan, Jessica L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salama, Mohamed E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, Benjamin L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peifer, MartinUNSPECIFIEDorcid.org/0000-0002-5243-5503UNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gertz, JasonUNSPECIFIEDorcid.org/0000-0001-7568-6789UNSPECIFIED
Johnson, Jane E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gazdar, Adi F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wechsler-Reya, Robert J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sos, Martin L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliver, Trudy G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-239825
DOI: 10.1016/j.ccell.2016.12.005
Journal or Publication Title: Cancer Cell
Volume: 31
Number: 2
Page Range: S. 270 - 286
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1878-3686
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MOUSE MODEL; N-MYC; TUMOR; LINES; CARCINOMAS; FAMILY; GENE; IDENTIFICATION; HETEROGENEITY; AMPLIFICATIONMultiple languages
Oncology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23982

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