Skip Nav Destination
Issues
1 October 2016
-
Cover Image
Cover Image
Gainor, Dardaei, and colleagues performed a molecular and functional analysis of repeat biopsies from patients with ALK-rearranged non–small cell lung cancer who developed ALK inhibitor resistance. ALK resistance mutations were more common after treatment with second-generation ALK inhibitors compared to treatment with the first-generation ALK inhibitor crizotinib, and each ALK inhibitor exhibited a specific spectrum of ALK resistance mutations. Identification of epithelial–mesenchymal transition (EMT) in a subset of second-generation ALK inhibitor–resistant biopsies suggested that EMT may contribute to second-generation ALK inhibitor resistance. The third-generation ALK inhibitor lorlatinib exhibited potency against single and compound ALK resistance mutations induced by second-generation ALK inhibitors. Together, these results describe the molecular mechanisms of resistance to first- and second-generation ALK inhibitors and highlight the importance of longitudinal sampling. For details, please see the article by Gainor, Dardaei, and colleagues on page 1118.Close Modal - PDF Icon PDF LinkTable of Contents
ISSN 2159-8274
EISSN 2159-8290
Issue Sections
In This Issue
In the Spotlight
Review
Research Articles
Author Choice
Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia
Marina Konopleva; Daniel A. Pollyea; Jalaja Potluri; Brenda Chyla; Leah Hogdal; Todd Busman; Evelyn McKeegan; Ahmed Hamed Salem; Ming Zhu; Justin L. Ricker; William Blum; Courtney D. DiNardo; Tapan Kadia; Martin Dunbar; Rachel Kirby; Nancy Falotico; Joel Leverson; Rod Humerickhouse; Mack Mabry; Richard Stone; Hagop Kantarjian; Anthony Letai
Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer
Justin F. Gainor; Leila Dardaei; Satoshi Yoda; Luc Friboulet; Ignaty Leshchiner; Ryohei Katayama; Ibiayi Dagogo-Jack; Shirish Gadgeel; Katherine Schultz; Manrose Singh; Emily Chin; Melissa Parks; Dana Lee; Richard H. DiCecca; Elizabeth Lockerman; Tiffany Huynh; Jennifer Logan; Lauren L. Ritterhouse; Long P. Le; Ashok Muniappan; Subba Digumarthy; Colleen Channick; Colleen Keyes; Gad Getz; Dora Dias-Santagata; Rebecca S. Heist; Jochen Lennerz; Lecia V. Sequist; Cyril H. Benes; A. John Iafrate; Mari Mino-Kenudson; Jeffrey A. Engelman; Alice T. Shaw
Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma
Tomoyo Okada; Ann Y. Lee; Li-Xuan Qin; Narasimhan Agaram; Takahiro Mimae; Yawei Shen; Rachael O'Connor; Miguel A. López-Lago; Amanda Craig; Martin L. Miller; Phaedra Agius; Evan Molinelli; Nicholas D. Socci; Aimee M. Crago; Fumi Shima; Chris Sander; Samuel Singer
Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia
Michael W.M. Kühn; Evelyn Song; Zhaohui Feng; Amit Sinha; Chun-Wei Chen; Aniruddha J. Deshpande; Monica Cusan; Noushin Farnoud; Annalisa Mupo; Carolyn Grove; Richard Koche; James E. Bradner; Elisa de Stanchina; George S. Vassiliou; Takayuki Hoshii; Scott A. Armstrong
Polarization of Tissue-Resident TFH-Like Cells in Human Hepatoma Bridges Innate Monocyte Inflammation and M2b Macrophage Polarization
Min-Min Chen; Xiao Xiao; Xiang-Ming Lao; Yuan Wei; Rui-Xian Liu; Qiu-Hui Zeng; Jun-Cheng Wang; Fang-Zhu Ouyang; Dong-Ping Chen; Ka-Wo Chan; Dai-Chao Shi; Limin Zheng; Dong-Ming Kuang
News in Brief
News in Depth
Research Watch
Breast Cancer
Drug Design
Drug Resistance
Epigenetics
Hepatocellular Carcinoma
Leukemia
Melanoma
Metabolism
Metastasis
Methylation
Prostate Cancer
Signaling
Structural Biology
Telomeres
Tumor Suppressor
Tumorigenesis
Advertisement