XSystematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer

Kim, Hyun Seok, Mendiratta, Saurabh, Kim, Jiyeon, Pecot, Chad Victor, Larsen, Jill E., Zubovych, Iryna, Seo, Bo Yeun, Kim, Jimi, Eskiocak, Banu, Chung, Hannah, McMillan, Elizabeth, Wu, Sherry, De Brabander, Jef, Komurov, Kakajan, Toombs, Jason E., Wei, Shuguang, Peyton, Michael, Williams, Noelle, Gazdar, Adi F., Posner, Bruce A., Brekken, Rolf A., Sood, Anil K., Deberardinis, Ralph J., Roth, Michael G., Minna, John D. and White, Michael A. (2013) XSystematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer. Cell, 155 3: 552-566. doi:10.1016/j.cell.2013.09.041

Author Kim, Hyun Seok
Mendiratta, Saurabh
Kim, Jiyeon
Pecot, Chad Victor
Larsen, Jill E.
Zubovych, Iryna
Seo, Bo Yeun
Kim, Jimi
Eskiocak, Banu
Chung, Hannah
McMillan, Elizabeth
Wu, Sherry
De Brabander, Jef
Komurov, Kakajan
Toombs, Jason E.
Wei, Shuguang
Peyton, Michael
Williams, Noelle
Gazdar, Adi F.
Posner, Bruce A.
Brekken, Rolf A.
Sood, Anil K.
Deberardinis, Ralph J.
Roth, Michael G.
Minna, John D.
White, Michael A.
Title XSystematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer
Journal name Cell   Check publisher's open access policy
ISSN 0092-8674
Publication date 2013-10-24
Sub-type Article (original research)
DOI 10.1016/j.cell.2013.09.041
Open Access Status Not yet assessed
Volume 155
Issue 3
Start page 552
End page 566
Total pages 15
Place of publication Cambridge, MA United States
Publisher Cell Press
Language eng
Abstract Context-specific molecular vulnerabilities that arise during tumor evolution represent an attractive intervention target class. However, the frequency and diversity of somatic lesions detected among lung tumors can confound efforts to identify these targets. To confront this challenge, we have applied parallel screening of chemical and genetic perturbations within a panel of molecularly annotated NSCLC lines to identify intervention opportunities tightly linked to molecular response indicators predictive of target sensitivity. Anchoring this analysis on a matched tumor/normal cell model from a lung adenocarcinoma patient identified three distinct target/response-indicator pairings that are represented with significant frequencies (6%-16%) in the patient population. These include NLRP3 mutation/inflammasome activation-dependent FLIP addiction, co-occurring KRAS and LKB1 mutation-driven COPI addiction, and selective sensitivity to a synthetic indolotriazine that is specified by a seven-gene expression signature. Target efficacies were validated in vivo, and mechanism-of-action studies informed generalizable principles underpinning cancer cell biology.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 73 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 27 Sep 2016, 20:08:53 EST by Jill Larsen on behalf of School of Medicine