Journal article

Mechanisms of Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancers

Ryohei Katayama, Alice T Shaw, Tahsin M Khan, Mari Mino-Kenudson, Benjamin J Solomon, Balazs Halmos, Nicholas A Jessop, John C Wain, Alan Tien Yeo, Cyril Benes, Lisa Drew, Jamal Carlos Saeh, Katherine Crosby, Lecia V Sequist, A John Iafrate, Jeffrey A Engelman

Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2012


Awarded by NIH

Awarded by National Cancer Institute (NCI)

Awarded by American Cancer Society

Awarded by NCI


Funding Acknowledgements

We thank T. Della Pelle at Massachusetts General Hospital (MGH) for help with the phospho-EGFR immunohistochemistry and E. Code, A. Wu, and S. Throner (Cancer Research, AstraZeneca R&D Boston) for help with the in vitro kinase assay experiments. Funding: This study was supported in part by a V Foundation for Cancer Research Translational Grant (J.A.E. and A. T. S.), NIH K08 grant CA120060-01 (J.A.E.), R01CA137008 (J.A.E.), R01CA140594 (J.A.E.), 1U01CA141457-01 (J.A.E.), National Cancer Institute (NCI) Lung SPORE P50CA090578 (J.A.E.), the Dana-Farber/Harvard Cancer Center, the American Association for Cancer Research (J.A.E.), American Cancer Society RSG-06-102-01-CCE (J.A.E.), the Ellison Foundation Scholar (J.A.E.), the American Lung Association (J.A.E.), Be a Part of the Solution philanthropy, friends and family of Ed and Judy Shanley, the Sig Adler Lung Cancer Research Fund, the MGH Thoracic Oncology Fund, and a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (R. K.). A. T. S. is the Charles W. and Jennifer C. Johnson Koch Institute Clinical Investigator. L. V. S. is supported by grants from Uniting Against Lung Cancer, sponsored by Uniting Against Lung Cancer: New England and the Marjorie E. Korff Fund, and from the NCI (R21CA156000). Author contributions: R. K. designed the experiments, performed cell line and in vitro studies, and wrote the manuscript. A. T. S. identified patients and obtained repeat biopsy samples, designed and supervised the experiments, and wrote the manuscript. T. M. K. performed cell line and in vitro studies. M.M.-K. performed and analyzed immunohistochemistry and pathology of all repeat biopsy samples. B.J.S., B. H., and L. V. S. identified patients and obtained repeat biopsy samples. N.A.J. organized specimen collection and genetic testing. J.C.W. performed biopsies on patients. A.T.Y. assisted R. K. in DNA sequence analysis. C. B. helped design experiments. L. D. and J.C.S. performed in vitro kinase assays and performed computational modeling. K. C. performed immunohistochemistry. A.J.I. supervised nucleic acid extraction and FISH testing. J.A.E. designed and supervised the experiments and wrote the manuscript. Competing interests: J.A.E. is a paid consultant for Ariad and Novartis; A.J.I. is a paid consultant for Pfizer and Abbott; A. T. S. is a paid consultant for Pfizer, Ariad, Chugai, and Novartis; B.J.S. has served on the advisory boards for Pfizer and Novartis. The other authors declare that they have no competing interests.