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1 July 2018
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Skoulidis, Goldberg, Greenawalt, and colleagues linked STK11 mutations to PD-1 inhibitor resistance in KRAS-mutant lung cancer. Patients with lung cancer harboring co-occurring STK11 and KRAS alterations had a lower response rate to PD-1/PD-L1 blockade than patients with co-occurring KRAS and TP53 alterations or KRAS mutations alone. STK11 alterations were enriched in PD-L1–negative tumors with an intermediate to high tumor mutation burden. However, STK11 alterations were also associated with primary resistance to PD-1 blockade in patients with PD-L1–positive tumors. Stk11 deletion induced de novo resistance to PD-1 inhibition in a mouse model of KRAS-mutant lung adenocarcinoma. These results demonstrate that STK11 alterations confer primary resistance to PD-1/PD-L1 blockade and suggest that genomic profiling may identify patients likely to benefit from PD-1 blockade. For details, please see the article by Skoulidis, Goldberg, Greenawalt, and colleagues on page 822. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Precision Prevention and Early Detection of Cancer: Fundamental Principles
Timothy R. Rebbeck; Karen Burns-White; Andrew T. Chan; Karen Emmons; Matthew Freedman; David J. Hunter; Peter Kraft; Francine Laden; Lorelei Mucci; Giovanni Parmigiani; Deborah Schrag; Sapna Syngal; Rulla M. Tamimi; Kasisomayajula Viswanath; Matthew B. Yurgelun; Judy E. Garber
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Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1–3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 Alterations
Sumanta K. Pal; Jonathan E. Rosenberg; Jean H. Hoffman-Censits; Raanan Berger; David I. Quinn; Matthew D. Galsky; Juergen Wolf; Christian Dittrich; Bhumsuk Keam; Jean-Pierre Delord; Jan H.M. Schellens; Gwenaelle Gravis; Jacques Medioni; Pablo Maroto; Virote Sriuranpong; Chaiyut Charoentum; Howard A. Burris; Viktor Grünwald; Daniel Petrylak; Ulka Vaishampayan; Eliahu Gez; Ugo De Giorgi; Jae-Lyun Lee; Jens Voortman; Sumati Gupta; Sunil Sharma; Amir Mortazavi; David J. Vaughn; Randi Isaacs; Katie Parker; Xueying Chen; Kun Yu; Dale Porter; Diana Graus Porta; Dean F. Bajorin
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STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma
Ferdinandos Skoulidis; Michael E. Goldberg; Danielle M. Greenawalt; Matthew D. Hellmann; Mark M. Awad; Justin F. Gainor; Alexa B. Schrock; Ryan J. Hartmaier; Sally E. Trabucco; Laurie Gay; Siraj M. Ali; Julia A. Elvin; Gaurav Singal; Jeffrey S. Ross; David Fabrizio; Peter M. Szabo; Han Chang; Ariella Sasson; Sujaya Srinivasan; Stefan Kirov; Joseph Szustakowski; Patrik Vitazka; Robin Edwards; Jose A. Bufill; Neelesh Sharma; Sai-Hong I. Ou; Nir Peled; David R. Spigel; Hira Rizvi; Elizabeth Jimenez Aguilar; Brett W. Carter; Jeremy Erasmus; Darragh F. Halpenny; Andrew J. Plodkowski; Niamh M. Long; Mizuki Nishino; Warren L. Denning; Ana Galan-Cobo; Haifa Hamdi; Taghreed Hirz; Pan Tong; Jing Wang; Jaime Rodriguez-Canales; Pamela A. Villalobos; Edwin R. Parra; Neda Kalhor; Lynette M. Sholl; Jennifer L. Sauter; Achim A. Jungbluth; Mari Mino-Kenudson; Roxana Azimi; Yasir Y. Elamin; Jianjun Zhang; Giulia C. Leonardi; Fei Jiang; Kwok-Kin Wong; J. Jack Lee; Vassiliki A. Papadimitrakopoulou; Ignacio I. Wistuba; Vincent A. Miller; Garrett M. Frampton; Jedd D. Wolchok; Alice T. Shaw; Pasi A. Jänne; Philip J. Stephens; Charles M. Rudin; William J. Geese; Lee A. Albacker; John V. Heymach
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Precision Targeted Therapy with BLU-667 for RET-Driven Cancers
Vivek Subbiah; Justin F. Gainor; Rami Rahal; Jason D. Brubaker; Joseph L. Kim; Michelle Maynard; Wei Hu; Qiongfang Cao; Michael P. Sheets; Douglas Wilson; Kevin J. Wilson; Lucian DiPietro; Paul Fleming; Michael Palmer; Mimi I. Hu; Lori Wirth; Marcia S. Brose; Sai-Hong Ignatius Ou; Matthew Taylor; Elena Garralda; Stephen Miller; Beni Wolf; Christoph Lengauer; Timothy Guzi; Erica K. Evans
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NF-κB–Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis
Paulo Rodrigues; Saroor A. Patel; Louise Harewood; Ioana Olan; Erika Vojtasova; Saiful E. Syafruddin; M. Nazhif Zaini; Emma K. Richardson; Johanna Burge; Anne Y. Warren; Grant D. Stewart; Kourosh Saeb-Parsy; Shamith A. Samarajiwa; Sakari Vanharanta
PTEN Deficiency and AMPK Activation Promote Nutrient Scavenging and Anabolism in Prostate Cancer Cells
Seong M. Kim; Tricia T. Nguyen; Archna Ravi; Peter Kubiniok; Brendan T. Finicle; Vaishali Jayashankar; Leonel Malacrida; Jue Hou; Jane Robertson; Dong Gao; Jonathan Chernoff; Michelle A. Digman; Eric O. Potma; Bruce J. Tromberg; Pierre Thibault; Aimee L. Edinger
CDK6 Antagonizes p53-Induced Responses during Tumorigenesis
Florian Bellutti; Anca-Sarmiza Tigan; Sofie Nebenfuehr; Marlies Dolezal; Markus Zojer; Reinhard Grausenburger; Svenja Hartenberger; Sebastian Kollmann; Eszter Doma; Michaela Prchal-Murphy; Iris Z. Uras; Alexander Höllein; Donna S. Neuberg; Benjamin L. Ebert; Anna Ringler; Andre C. Mueller; Joanna I. Loizou; Philip W. Hinds; Claus Vogl; Gerwin Heller; Stefan Kubicek; Johannes Zuber; Marcos Malumbres; Matthias Farlik; Andreas Villunger; Karoline Kollmann; Veronika Sexl
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