Cancer Research Annual Meeting 2010 Genetics and Biology of Brain Cancer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kobayashi, S.
Right arrow Articles by Halmos, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kobayashi, S.
Right arrow Articles by Halmos, B.
[Cancer Research 65, 7096-7101, August 15, 2005]
© 2005 American Association for Cancer Research

Priority Reports

An Alternative Inhibitor Overcomes Resistance Caused by a Mutation of the Epidermal Growth Factor Receptor

Susumu Kobayashi1, Hongbin Ji2, Yuki Yuza2, Matthew Meyerson2, Kwok-Kin Wong2, Daniel G. Tenen1 and Balázs Halmos1,3

1 Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School; 2 Departments of Medical Oncology and Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts; and 3 University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio

Requests for reprints: Daniel G. Tenen, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115. Phone: 617-667-5561; Fax: 617-667-3299; E-mail: dtenen{at}bidmc.harvard.edu.

Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in non–small cell lung cancer specimens from patients responding to anilinoquinazoline EGFR inhibitors. However, clinical resistance to EGFR inhibitor therapy is commonly observed. Previously, we showed that such resistance can be caused by a second mutation of the EGFR gene, leading to a T790M amino acid change in the EGFR tyrosine kinase domain and also found that CL-387,785, a specific and irreversible anilinoquinazoline EGFR inhibitor, was able to overcome this resistance on the biochemical level. Here, we present the successful establishment of a stable Ba/F3 cell line model system for the study of oncogenic EGFR signaling and the functional consequences of the EGFR T790M resistance mutation. We show the ability of gefitinib to induce growth arrest and apoptosis in cells transfected with wild-type or L858R EGFR, whereas the T790M mutation leads to high-level functional resistance against gefitinib and erlotinib. In addition, CL-387,785 is able to overcome resistance caused by the T790M mutation on a functional level, correlating with effective inhibition of downstream signaling pathways. Similar data was also obtained with the use of the gefitinib-resistant H1975 lung cancer cell line. The systems established by us should prove useful for the large-scale screening of alternative EGFR inhibitor compounds against the T790M or other EGFR mutations. These data also support the notion that clinical investigations of compounds similar to CL-387,785 may be useful as a treatment strategy for patients with resistance to EGFR inhibitor therapy caused by the T790M mutation.




This article has been cited by other articles:


Home page
 Mol Cancer ResHome page
J. K. Rho, Y. J. Choi, J. K. Lee, B.-Y. Ryoo, I. I. Na, S. H. Yang, S. S. Lee, C. H. Kim, Y. D. Yoo, and J. C. Lee
The Role of MET Activation in Determining the Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Mol. Cancer Res., October 1, 2009; 7(10): 1736 - 1743.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. N. Naumov, M. B. Nilsson, T. Cascone, A. Briggs, O. Straume, L. A. Akslen, E. Lifshits, L. A. Byers, L. Xu, H.-k. Wu, et al.
Combined Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor (EGFR) Blockade Inhibits Tumor Growth in Xenograft Models of EGFR Inhibitor Resistance
Clin. Cancer Res., May 15, 2009; 15(10): 3484 - 3494.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. K. Kancha, N. von Bubnoff, C. Peschel, and J. Duyster
Functional Analysis of Epidermal Growth Factor Receptor (EGFR) Mutations and Potential Implications for EGFR Targeted Therapy
Clin. Cancer Res., January 15, 2009; 15(2): 460 - 467.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. B. Costa, K.-S. H. Nguyen, B. C. Cho, L. V. Sequist, D. M. Jackman, G. J. Riely, B. Y. Yeap, B. Halmos, J. H. Kim, P. A. Janne, et al.
Effects of Erlotinib in EGFR Mutated Non-Small Cell Lung Cancers with Resistance to Gefitinib
Clin. Cancer Res., November 1, 2008; 14(21): 7060 - 7067.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Shimamura, D. Li, H. Ji, H. J. Haringsma, E. Liniker, C. L. Borgman, A. M. Lowell, Y. Minami, K. McNamara, S. A. Perera, et al.
Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Cancer Res., July 15, 2008; 68(14): 5827 - 5838.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
P. S. Hodkinson, A. MacKinnon, and T. Sethi
Targeting Growth Factors in Lung Cancer
Chest, May 1, 2008; 133(5): 1209 - 1216.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
M. Scaltriti and J. Baselga
The Epidermal Growth Factor Receptor Pathway: A Model for Targeted Therapy
Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 91 - 98.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
N. Godin-Heymann, L. Ulkus, B. W. Brannigan, U. McDermott, J. Lamb, S. Maheswaran, J. Settleman, and D. A. Haber
The T790M "gatekeeper" mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor
Mol. Cancer Ther., April 1, 2008; 7(4): 874 - 879.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
H.-P. Kim, S.-W. Han, S.-H. Kim, S.-A. Im, D.-Y. Oh, Y.-J. Bang, and T.-Y. Kim
Combined lapatinib and cetuximab enhance cytotoxicity against gefitinib-resistant lung cancer cells
Mol. Cancer Ther., March 1, 2008; 7(3): 607 - 615.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Bean, C. Brennan, J.-Y. Shih, G. Riely, A. Viale, L. Wang, D. Chitale, N. Motoi, J. Szoke, S. Broderick, et al.
MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib
PNAS, December 26, 2007; 104(52): 20932 - 20937.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Deng, T. Shimamura, S. Perera, N. E. Carlson, D. Cai, G. I. Shapiro, K.-K. Wong, and A. Letai
Proapoptotic BH3-Only BCL-2 Family Protein BIM Connects Death Signaling from Epidermal Growth Factor Receptor Inhibition to the Mitochondrion
Cancer Res., December 15, 2007; 67(24): 11867 - 11875.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Z. Yu, T. J. Boggon, S. Kobayashi, C. Jin, P. C. Ma, A. Dowlati, J. A. Kern, D. G. Tenen, and B. Halmos
Resistance to an Irreversible Epidermal Growth Factor Receptor (EGFR) Inhibitor in EGFR-Mutant Lung Cancer Reveals Novel Treatment Strategies
Cancer Res., November 1, 2007; 67(21): 10417 - 10427.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. F. Doody, Y. Wang, S. N. Patel, C. Joynes, S. P. Lee, J. Gerlak, R. L. Rolser, Y. Li, P. Steiner, R. Bassi, et al.
Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non small cell lung cancers
Mol. Cancer Ther., October 1, 2007; 6(10): 2642 - 2651.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Ogino, H. Kitao, S. Hirano, A. Uchida, M. Ishiai, T. Kozuki, N. Takigawa, M. Takata, K. Kiura, and M. Tanimoto
Emergence of Epidermal Growth Factor Receptor T790M Mutation during Chronic Exposure to Gefitinib in a Non Small Cell Lung Cancer Cell Line
Cancer Res., August 15, 2007; 67(16): 7807 - 7814.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Godin-Heymann, I. Bryant, M. N. Rivera, L. Ulkus, D. W. Bell, D. J. Riese II, J. Settleman, and D. A. Haber
Oncogenic Activity of Epidermal Growth Factor Receptor Kinase Mutant Alleles Is Enhanced by the T790M Drug Resistance Mutation
Cancer Res., August 1, 2007; 67(15): 7319 - 7326.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. E. Little, D. A. Bax, M. Rodriguez-Pinilla, R. Natrajan, B. Messahel, K. Pritchard-Jones, G. M. Vujanic, J. S. Reis-Filho, and C. Jones
Multifaceted Dysregulation of the Epidermal Growth Factor Receptor Pathway in Clear Cell Sarcoma of the Kidney
Clin. Cancer Res., August 1, 2007; 13(15): 4360 - 4364.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. de La Motte Rouge, L. Galluzzi, K. A. Olaussen, Y. Zermati, E. Tasdemir, T. Robert, H. Ripoche, V. Lazar, P. Dessen, F. Harper, et al.
A Novel Epidermal Growth Factor Receptor Inhibitor Promotes Apoptosis in Non-Small Cell Lung Cancer Cells Resistant to Erlotinib
Cancer Res., July 1, 2007; 67(13): 6253 - 6262.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
P. A. Bunn Jr
Can Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Be Overcome by Different Small-Molecule Tyrosine Kinase Inhibitors?
J. Clin. Oncol., June 20, 2007; 25(18): 2504 - 2505.
[Full Text] [PDF]

Home page
 JCOHome page
B. C. Cho, C.-K. Im, M.-S. Park, S. K. Kim, J. Chang, J. P. Park, H. J. Choi, Y. J. Kim, S.-J. Shin, J. H. Sohn, et al.
Phase II Study of Erlotinib in Advanced Non-Small-Cell Lung Cancer After Failure of Gefitinib
J. Clin. Oncol., June 20, 2007; 25(18): 2528 - 2533.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Mounawar, A. Mukeria, F. Le Calvez, R. J. Hung, H. Renard, A. Cortot, C. Bollart, D. Zaridze, P. Brennan, P. Boffetta, et al.
Patterns of EGFR, HER2, TP53, and KRAS Mutations of p14arf Expression in Non-Small Cell Lung Cancers in Relation to Smoking History
Cancer Res., June 15, 2007; 67(12): 5667 - 5672.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. B. Gendreau, R. Ventura, P. Keast, A. D. Laird, F. M. Yakes, W. Zhang, F. Bentzien, B. Cancilla, J. Lutman, F. Chu, et al.
Inhibition of the T790M Gatekeeper Mutant of the Epidermal Growth Factor Receptor by EXEL-7647
Clin. Cancer Res., June 15, 2007; 13(12): 3713 - 3723.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Li, Y.-H. Ling, I. D. Goldman, and R. Perez-Soler
Schedule-Dependent Cytotoxic Synergism of Pemetrexed and Erlotinib in Human Non-Small Cell Lung Cancer Cells
Clin. Cancer Res., June 1, 2007; 13(11): 3413 - 3422.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Okabe, I. Okamoto, K. Tamura, M. Terashima, T. Yoshida, T. Satoh, M. Takada, M. Fukuoka, and K. Nakagawa
Differential Constitutive Activation of the Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer Cells Bearing EGFR Gene Mutation and Amplification
Cancer Res., March 1, 2007; 67(5): 2046 - 2053.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Mulloy, A. Ferrand, Y. Kim, R. Sordella, D. W. Bell, D. A. Haber, K. S. Anderson, and J. Settleman
Epidermal Growth Factor Receptor Mutants from Human Lung Cancers Exhibit Enhanced Catalytic Activity and Increased Sensitivity to Gefitinib
Cancer Res., March 1, 2007; 67(5): 2325 - 2330.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. Steiner, C. Joynes, R. Bassi, S. Wang, J. R. Tonra, Y. R. Hadari, and D. J. Hicklin
Tumor Growth Inhibition with Cetuximab and Chemotherapy in Non-Small Cell Lung Cancer Xenografts Expressing Wild-type and Mutated Epidermal Growth Factor Receptor
Clin. Cancer Res., March 1, 2007; 13(5): 1540 - 1551.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Kobayashi, T. Shimamura, S. Monti, U. Steidl, C. J. Hetherington, A. M. Lowell, T. Golub, M. Meyerson, D. G. Tenen, G. I. Shapiro, et al.
Transcriptional Profiling Identifies Cyclin D1 as a Critical Downstream Effector of Mutant Epidermal Growth Factor Receptor Signaling
Cancer Res., December 1, 2006; 66(23): 11389 - 11398.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. N. Balak, Y. Gong, G. J. Riely, R. Somwar, A. R. Li, M. F. Zakowski, A. Chiang, G. Yang, O. Ouerfelli, M. G. Kris, et al.
Novel D761Y and Common Secondary T790M Mutations in Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinomas with Acquired Resistance to Kinase Inhibitors.
Clin. Cancer Res., November 1, 2006; 12(21): 6494 - 6501.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Giaccone, M. Gallegos Ruiz, T. Le Chevalier, N. Thatcher, E. Smit, J. A. Rodriguez, P. Janne, D. Oulid-Aissa, and J.-C. Soria
Erlotinib for Frontline Treatment of Advanced Non-Small Cell Lung Cancer: a Phase II Study.
Clin. Cancer Res., October 15, 2006; 12(20): 6049 - 6055.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Su, C. Bodenstein, R. A. Dumont, Y. Seimbille, S. Dubinett, M. E. Phelps, H. Herschman, J. Czernin, and W. Weber
Monitoring Tumor Glucose Utilization by Positron Emission Tomography for the Prediction of Treatment Response to Epidermal Growth Factor Receptor Kinase Inhibitors.
Clin. Cancer Res., October 1, 2006; 12(19): 5659 - 5667.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Scaltriti and J. Baselga
The epidermal growth factor receptor pathway: a model for targeted therapy.
Clin. Cancer Res., September 15, 2006; 12(18): 5268 - 5272.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. L. Kwak, J. Jankowski, S. P. Thayer, G. Y. Lauwers, B. W. Brannigan, P. L. Harris, R. A. Okimoto, S. M. Haserlat, D. R. Driscoll, D. Ferry, et al.
Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas.
Clin. Cancer Res., July 15, 2006; 12(14): 4283 - 4287.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. K. Thomas, B. Weir, and M. Meyerson
Genomic approaches to lung cancer.
Clin. Cancer Res., July 15, 2006; 12(14): 4384s - 4391s.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
J. Baselga
Targeting Tyrosine Kinases in Cancer: The Second Wave.
Science, May 26, 2006; 312(5777): 1175 - 1178.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
E. Calvo and J. Baselga
Ethnic Differences in Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
J. Clin. Oncol., May 10, 2006; 24(14): 2158 - 2163.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. R. Jett and Y. E. Miller
Update in lung cancer 2005.
Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 695 - 697.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2005 by the American Association for Cancer Research.