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1 January 2017
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Jeong and colleagues developed mouse models of lung squamous cell carcinoma (LSCC) driven by Trp53 loss with or without Keap1 loss to further elucidate the role of the KEAP1/NRF2 pathway in LSCC and identify the LSCC cell of origin. Deletion of Trp53 and codeletion of Trp53 and Keap1 in peripheral lung cells or in tracheal epithelial cells gave rise, respectively, to lung adenocarcinomas or LSCCs, and codeletion of Trp53 and Keap1 resulted in the development of LSCCs from airway basal stem cells that were more proliferative and more resistant to radiation and oxidative stress, and exhibited decreased intracellular reactive oxygen species compared with Trp53−/− LSCCs. Moreover, KEAP1 mutation status in LSCCs and lung adenocarcinomas could be detected in circulating tumor DNA and predicted patient response to radiotherapy. These findings show how the genetic mouse models of LSCC enabled the identification of the LSCC cell of origin and the characterization of the role of the KEAP1/NRF2 pathway in LSCC. For details, please see the article by Jeong and colleagues on page 86. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas
Yanwen Jiang; Ana Ortega-Molina; Huimin Geng; Hsia-Yuan Ying; Katerina Hatzi; Sara Parsa; Dylan McNally; Ling Wang; Ashley S. Doane; Xabier Agirre; Matt Teater; Cem Meydan; Zhuoning Li; David Poloway; Shenqiu Wang; Daisuke Ennishi; David W. Scott; Kristy R. Stengel; Janice E. Kranz; Edward Holson; Sneh Sharma; James W. Young; Chi-Shuen Chu; Robert G. Roeder; Rita Shaknovich; Scott W. Hiebert; Randy D. Gascoyne; Wayne Tam; Olivier Elemento; Hans-Guido Wendel; Ari M. Melnick
The Master Neural Transcription Factor BRN2 Is an Androgen Receptor–Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer
Jennifer L. Bishop; Daksh Thaper; Sepideh Vahid; Alastair Davies; Kirsi Ketola; Hidetoshi Kuruma; Randy Jama; Ka Mun Nip; Arkhjamil Angeles; Fraser Johnson; Alexander W. Wyatt; Ladan Fazli; Martin E. Gleave; Dong Lin; Mark A. Rubin; Colin C. Collins; Yuzhuo Wang; Himisha Beltran; Amina Zoubeidi
Tumor Cell–Independent Estrogen Signaling Drives Disease Progression through Mobilization of Myeloid-Derived Suppressor Cells
Nikolaos Svoronos; Alfredo Perales-Puchalt; Michael J. Allegrezza; Melanie R. Rutkowski; Kyle K. Payne; Amelia J. Tesone; Jenny M. Nguyen; Tyler J. Curiel; Mark G. Cadungog; Sunil Singhal; Evgeniy B. Eruslanov; Paul Zhang; Julia Tchou; Rugang Zhang; Jose R. Conejo-Garcia
Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance
Youngtae Jeong; Ngoc T. Hoang; Alexander Lovejoy; Henning Stehr; Aaron M. Newman; Andrew J. Gentles; William Kong; Diana Truong; Shanique Martin; Aadel Chaudhuri; Diane Heiser; Li Zhou; Carmen Say; Justin N. Carter; Susan M. Hiniker; Billy W. Loo, Jr; Robert B. West; Philip Beachy; Ash A. Alizadeh; Maximilian Diehn
A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors
Cristina Saura; Desamparados Roda; Susana Roselló; Mafalda Oliveira; Teresa Macarulla; José Alejandro Pérez-Fidalgo; Rafael Morales-Barrera; Juan Manuel Sanchis-García; Luna Musib; Nageshwar Budha; Jin Zhu; Michelle Nannini; Wai Y. Chan; Sandra M. Sanabria Bohórquez; Raymond D. Meng; Kui Lin; Yibing Yan; Premal Patel; José Baselga; Josep Tabernero; Andrés Cervantes
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