EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors
Top Cited Papers
- 28 October 2010
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 363 (18), 1734-1739
- https://doi.org/10.1056/nejmoa1007478
Abstract
The EML4 (echinoderm microtubule-associated protein-like 4)–ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non–small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.)Keywords
This publication has 20 references indexed in Scilit:
- EML4-ALK: Honing In on a New Target in Non–Small-Cell Lung CancerJournal of Clinical Oncology, 2009
- Gefitinib or Carboplatin–Paclitaxel in Pulmonary AdenocarcinomaThe New England Journal of Medicine, 2009
- A mouse model for EML4-ALK -positive lung cancerProceedings of the National Academy of Sciences of the United States of America, 2008
- Non‐solid oncogenes in solid tumors: EML4–ALK fusion genes in lung cancerCancer Science, 2008
- Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancerNature, 2007
- Identification of a constitutively active mutant of JAK3 by retroviral expression screeningLeukemia Research, 2007
- EGFRMutation and Resistance of Non–Small-Cell Lung Cancer to GefitinibThe New England Journal of Medicine, 2005
- Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase DomainPLoS Medicine, 2005
- Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemiaCancer Cell, 2002
- Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid LeukemiaThe New England Journal of Medicine, 2001