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Science 304 (5676): 1458-1461

Copyright © 2004 by the American Association for the Advancement of Science

A Bull's Eye for Targeted Lung Cancer Therapy

John D. Minna, Adi F. Gazdar, Stephen R. Sprang, Joachim Herz

The tyrosine kinase inhibitor gefitinib has had mixed results in the treatment of lung cancer. The reason is now revealed in two papers published here (Paez et al.) and elsewhere, which receive in-depth discussion in a Perspective by Minna et al. The two new studies show that tumors from a subset of lung cancer patients with an efficacious response to gefitinib carry mutations in the kinase domain of the EGF receptor. The new findings should enable early selection of those lung cancer patients most likely to respond well to gefitinib.

J. D. Minna is in the Departments of Internal Medicine and Pharmacology and A. F. Gazdar is in the Department of Pathology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. S. R. Sprang is in the Howard Hughes Medical Institute, Department of Biochemistry, and J. Herz is in the Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. E-mail: john.minna{at}

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Clin. Cancer Res. 20, 531-539
   Abstract »    Full Text »    PDF »
Src Mediates Cigarette Smoke-Induced Resistance to Tyrosine Kinase Inhibitors in NSCLC Cells.
S. Filosto, D. S. Baston, S. Chung, C. R. Becker, and T. Goldkorn (2013)
Mol. Cancer Ther. 12, 1579-1590
   Abstract »    Full Text »    PDF »
Cigarette Smoke Induces Aberrant EGF Receptor Activation That Mediates Lung Cancer Development and Resistance to Tyrosine Kinase Inhibitors.
S. Filosto, C. R. Becker, and T. Goldkorn (2012)
Mol. Cancer Ther. 11, 795-804
   Abstract »    Full Text »    PDF »
Characterizing the Clinical Relevance of an Embryonic Stem Cell Phenotype in Lung Adenocarcinoma.
M. Stevenson, W. Mostertz, C. Acharya, W. Kim, K. Walters, W. Barry, K. Higgins, S. A. Tuchman, J. Crawford, G. Vlahovic, et al. (2009)
Clin. Cancer Res. 15, 7553-7561
   Abstract »    Full Text »    PDF »
Review Article: A Reevaluation of the Clinical Significance of Histological Subtyping of Non--Small-Cell Lung Carcinoma: Diagnostic Algorithms in the Era of Personalized Treatments.
G. Rossi, G. Pelosi, P. Graziano, M. Barbareschi, and M. Papotti (2009)
International Journal of Surgical Pathology 17, 206-218
   Abstract »    PDF »
Response to trastuzumab, erlotinib, and bevacizumab, alone and in combination, is correlated with the level of human epidermal growth factor receptor-2 expression in human breast cancer cell lines.
D. R. Emlet, K. A. Brown, D. L. Kociban, A. A. Pollice, C. A. Smith, B. B. L. Ong, and S. E. Shackney (2007)
Mol. Cancer Ther. 6, 2664-2674
   Abstract »    Full Text »    PDF »
Lipid rafts are required for Kit survival and proliferation signals.
T. Jahn, E. Leifheit, S. Gooch, S. Sindhu, and K. Weinberg (2007)
Blood 110, 1739-1747
   Abstract »    Full Text »    PDF »
Oxygen Concentration Determines the Biological Effects of NOTCH-1 Signaling in Adenocarcinoma of the Lung.
Y. Chen, M. A. De Marco, I. Graziani, A. F. Gazdar, P. R. Strack, L. Miele, and M. Bocchetta (2007)
Cancer Res. 67, 7954-7959
   Abstract »    Full Text »    PDF »
Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non-Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial.
U. Gatzemeier, A. Pluzanska, A. Szczesna, E. Kaukel, J. Roubec, F. De Rosa, J. Milanowski, H. Karnicka-Mlodkowski, M. Pesek, P. Serwatowski, et al. (2007)
J. Clin. Oncol. 25, 1545-1552
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Targeted therapies in combination with chemotherapy in non-small cell lung cancer..
D. H. Johnson (2006)
Clin. Cancer Res. 12, 4451s-4457s
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Differential Gene Expression Analysis Reveals Generation of an Autocrine Loop by a Mutant Epidermal Growth Factor Receptor in Glioma Cells.
D. B. Ramnarain, S. Park, D. Y. Lee, K. J. Hatanpaa, S. O. Scoggin, H. Otu, T. A. Libermann, J. M. Raisanen, R. Ashfaq, E. T. Wong, et al. (2006)
Cancer Res. 66, 867-874
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Clinicopathologic Significance of the Mutations of the Epidermal Growth Factor Receptor Gene in Patients with Non-Small Cell Lung Cancer.
Y. Tomizawa, H. Iijima, N. Sunaga, K. Sato, A. Takise, Y. Otani, S. Tanaka, T. Suga, R. Saito, T. Ishizuka, et al. (2005)
Clin. Cancer Res. 11, 6816-6822
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Gefitinib in Colorectal Cancer: If Wishes Were Horses.
C. D. Blanke (2005)
J. Clin. Oncol. 23, 5446-5449
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Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients.
H. Cortes-Funes, C. Gomez, R. Rosell, P. Valero, C. Garcia-Giron, A. Velasco, A. Izquierdo, P. Diz, C. Camps, D. Castellanos, et al. (2005)
Ann. Onc. 16, 1081-1086
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Clinical and Biological Features Associated With Epidermal Growth Factor Receptor Gene Mutations in Lung Cancers.
H. Shigematsu, L. Lin, T. Takahashi, M. Nomura, M. Suzuki, I. I. Wistuba, K. M. Fong, H. Lee, S. Toyooka, N. Shimizu, et al. (2005)
J Natl Cancer Inst 97, 339-346
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Pulsatile Administration of the Epidermal Growth Factor Receptor Inhibitor Gefitinib Is Significantly More Effective than Continuous Dosing for Sensitizing Tumors to Paclitaxel.
D. B. Solit, Y. She, J. Lobo, M. G. Kris, H. I. Scher, N. Rosen, and F. M. Sirotnak (2005)
Clin. Cancer Res. 11, 1983-1989
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