EGFR Mutation and Resistance of Non-Small-Cell Lung Cancer to Gefitinib

doi:10.1056/NEJMoa044238

Volume 352:786-792		February 24, 2005		Number 8

EGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib

Susumu Kobayashi, M.D., Ph.D., Titus J. Boggon, Ph.D., Tajhal Dayaram, B.A., Pasi A. Jänne, M.D., Ph.D., Olivier Kocher, M.D., Ph.D., Matthew Meyerson, M.D., Ph.D., Bruce E. Johnson, M.D., Michael J. Eck, M.D., Ph.D., Daniel G. Tenen, M.D., and Balázs Halmos, M.D.

Full Text

PDF

PDA Full Text

PowerPoint Slide Set

Editorial
by Dowell, J. E.

Letters

Add to Personal Archive

Add to Citation Manager

Notify a Friend

E-mail When Cited

E-mail When Letters Appear

PubMed Citation

SUMMARY

Mutations of the epidermal growth factor receptor (EGFR) genehave been identified in specimens from patients with non–small-celllung cancer who have a response to anilinoquinazoline EGFR inhibitors.Despite the dramatic responses to such inhibitors, most patientsultimately have a relapse. The mechanism of the drug resistanceis unknown. Here we report the case of a patient with EGFR-mutant,gefitinib-responsive, advanced non–small-cell lung cancerwho had a relapse after two years of complete remission duringtreatment with gefitinib. The DNA sequence of the EGFR genein his tumor biopsy specimen at relapse revealed the presenceof a second point mutation, resulting in threonine-to-methionineamino acid change at position 790 of EGFR. Structural modelingand biochemical studies showed that this second mutation ledto gefitinib resistance.

Source Information

From the Division of Hematology/Oncology (S.K., T.D., D.G.T., B.H.) and the Department of Pathology (O.K.), Beth Israel Deaconess Medical Center, Harvard Medical School; the Departments of Cancer Biology (T.J.B., M.J.E.), Medical Oncology (P.A.J., B.E.J., M.M.), and Pathology (M.M.), Dana–Farber Cancer Institute, Harvard Medical School; the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School (T.J.B., M.J.E.); and the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School (P.A.J., B.E.J.) — all in Boston; and the Ireland Cancer Center, University Hospitals of Cleveland, Case School of Medicine, Cleveland (B.H.).

Address reprint requests to Dr. Tenen at the Harvard Institutes of Medicine, HIM-954, 77 Louis Pasteur Ave., Boston, MA 02215, or at dtenen{at}bidmc.harvard.edu.

Full Text of this Article

Related Letters:

EGFR Mutation and Response of Lung Cancer to Gefitinib
Toyooka S., Kiura K., Mitsudomi T., Kobayashi S., Tenen D. G., Halmos B.
Extract | Full Text | PDF
N Engl J Med 2005; 352:2136, May 19, 2005. Correspondence

This article has been cited by other articles:

Shimamura, T., Li, D., Ji, H., Haringsma, H. J., Liniker, E., Borgman, C. L., Lowell, A. M., Minami, Y., McNamara, K., Perera, S. A., Zaghlul, S., Thomas, R. K., Greulich, H., Kobayashi, S., Chirieac, L. R., Padera, R. F., Kubo, S., Takahashi, M., Tenen, D. G., Meyerson, M., Wong, K.-K., Shapiro, G. I. (2008). Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance. Cancer Res. 68: 5827-5838 [Abstract] [Full Text]
Villalona-Calero, M. A., Otterson, G. A., Wientjes, M. G., Weber, F., Bekaii-Saab, T., Young, D., Murgo, A. J., Jensen, R., Yeh, T.-K., Wei, Y., Zhang, Y., Eng, C., Grever, M., Au, J. L.-S. (2008). Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer: a phase II study. Ann Oncol 0: mdn412v1-mdn412 [Abstract] [Full Text]
Llovet, J. M., Di Bisceglie, A. M., Bruix, J., Kramer, B. S., Lencioni, R., Zhu, A. X., Sherman, M., Schwartz, M., Lotze, M., Talwalkar, J., Gores, G. J., for the Panel of Experts in HCC-Design Clinical Tr, (2008). Design and Endpoints of Clinical Trials in Hepatocellular Carcinoma. JNCI J Natl Cancer Inst 100: 698-711 [Abstract] [Full Text]
Sequist, L. V., Martins, R. G., Spigel, D., Grunberg, S. M., Spira, A., Janne, P. A., Joshi, V. A., McCollum, D., Evans, T. L., Muzikansky, A., Kuhlmann, G. L., Han, M., Goldberg, J. S., Settleman, J., Iafrate, A. J., Engelman, J. A., Haber, D. A., Johnson, B. E., Lynch, T. J. (2008). First-Line Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer Harboring Somatic EGFR Mutations. JCO 26: 2442-2449 [Abstract] [Full Text]
Shepherd, F. A. (2008). Molecular Selection of Patients for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer With Epidermal Growth Factor Inhibitors: Not Quite Ready for Prime Time. JCO 26: 2426-2427 [Full Text]
Engelman, J. A., Janne, P. A. (2008). Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. Clin. Cancer Res. 14: 2895-2899 [Abstract] [Full Text]
Zucali, P. A., Ruiz, M. G., Giovannetti, E., Destro, A., Varella-Garcia, M., Floor, K., Ceresoli, G. L., Rodriguez, J. A., Garassino, I., Comoglio, P., Roncalli, M., Santoro, A., Giaccone, G. (2008). Role of cMET expression in non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors. Ann Oncol 0: mdn240v1-mdn240 [Abstract] [Full Text]
Weinstein, I. B., Joe, A., Felsher, D. (2008). Oncogene Addiction. Cancer Res. 68: 3077-3080 [Abstract] [Full Text]
Hodkinson, P. S., MacKinnon, A., Sethi, T. (2008). Targeting Growth Factors in Lung Cancer. Chest 133: 1209-1216 [Abstract] [Full Text]
Wang, Y.-C., Kulp, S. K., Wang, D., Yang, C.-C., Sargeant, A. M., Hung, J.-H., Kashida, Y., Yamaguchi, M., Chang, G.-D., Chen, C.-S. (2008). Targeting Endoplasmic Reticulum Stress and Akt with OSU-03012 and Gefitinib or Erlotinib to Overcome Resistance to Epidermal Growth Factor Receptor Inhibitors. Cancer Res. 68: 2820-2830 [Abstract] [Full Text]
Trowe, T., Boukouvala, S., Calkins, K., Cutler, R. E. Jr., Fong, R., Funke, R., Gendreau, S. B., Kim, Y. D., Miller, N., Woolfrey, J. R., Vysotskaia, V., Yang, J. P., Gerritsen, M. E., Matthews, D. J., Lamb, P., Heuer, T. S. (2008). EXEL-7647 Inhibits Mutant Forms of ErbB2 Associated with Lapatinib Resistance and Neoplastic Transformation. Clin. Cancer Res. 14: 2465-2475 [Abstract] [Full Text]
Kumar, A., Petri, E. T., Halmos, B., Boggon, T. J. (2008). Structure and Clinical Relevance of the Epidermal Growth Factor Receptor in Human Cancer. JCO 26: 1742-1751 [Abstract] [Full Text]
Godin-Heymann, N., Ulkus, L., Brannigan, B. W., McDermott, U., Lamb, J., Maheswaran, S., Settleman, J., Haber, D. A. (2008). The T790M "gatekeeper" mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor. Molecular Cancer Therapeutics 7: 874-879 [Abstract] [Full Text]
Smith, G D, Chadwick, B E, Willmore-Payne, C, Bentz, J S (2008). Detection of epidermal growth factor receptor gene mutations in cytology specimens from patients with non-small cell lung cancer utilising high-resolution melting amplicon analysis. J. Clin. Pathol. 61: 487-493 [Abstract] [Full Text]
Torkamani, A., Schork, N. J. (2008). Prediction of Cancer Driver Mutations in Protein Kinases. Cancer Res. 68: 1675-1682 [Abstract] [Full Text]
Peipp, M., Schneider-Merck, T., Dechant, M., Beyer, T., Lammerts van Bueren, J. J., Bleeker, W. K., Parren, P. W. H. I., van de Winkel, J. G. J., Valerius, T. (2008). Tumor Cell Killing Mechanisms of Epidermal Growth Factor Receptor (EGFR) Antibodies Are Not Affected by Lung Cancer-Associated EGFR Kinase Mutations. J. Immunol. 180: 4338-4345 [Abstract] [Full Text]
Ciardiello, F., Tortora, G. (2008). EGFR Antagonists in Cancer Treatment. NEJM 358: 1160-1174 [Full Text]
Costa, D. B., Schumer, S. T., Tenen, D. G., Kobayashi, S. (2008). Differential Responses to Erlotinib in Epidermal Growth Factor Receptor (EGFR)-Mutated Lung Cancers With Acquired Resistance to Gefitinib Carrying the L747S or T790M Secondary Mutations. JCO 26: 1182-1184 [Full Text]
Cho, B. C., Kim, J. H. (2008). In Reply. JCO 26: 1184-1186 [Full Text]
Kim, H.-P., Han, S.-W., Kim, S.-H., Im, S.-A., Oh, D.-Y., Bang, Y.-J., Kim, T.-Y. (2008). Combined lapatinib and cetuximab enhance cytotoxicity against gefitinib-resistant lung cancer cells. Molecular Cancer Therapeutics 7: 607-615 [Abstract] [Full Text]
Burris, H. III, Rocha-Lima, C. (2008). New Therapeutic Directions for Advanced Pancreatic Cancer: Targeting the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways. The Oncologist 13: 289-298 [Abstract] [Full Text]
Yun, C.-H., Mengwasser, K. E., Toms, A. V., Woo, M. S., Greulich, H., Wong, K.-K., Meyerson, M., Eck, M. J. (2008). The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc. Natl. Acad. Sci. USA 105: 2070-2075 [Abstract] [Full Text]
Cavazzoni, A., Alfieri, R. R., Carmi, C., Zuliani, V., Galetti, M., Fumarola, C., Frazzi, R., Bonelli, M., Bordi, F., Lodola, A., Mor, M., Petronini, P. G. (2008). Dual mechanisms of action of the 5-benzylidene-hydantoin UPR1024 on lung cancer cell lines. Molecular Cancer Therapeutics 7: 361-370 [Abstract] [Full Text]
MacLaine, N. J., Wood, M. D., Holder, J. C., Rees, R. W., Southgate, J. (2008). Sensitivity of Normal, Paramalignant, and Malignant Human Urothelial Cells to Inhibitors of the Epidermal Growth Factor Receptor Signaling Pathway. Mol Cancer Res 6: 53-63 [Abstract] [Full Text]
Bean, J., Brennan, C., Shih, J.-Y., Riely, G., Viale, A., Wang, L., Chitale, D., Motoi, N., Szoke, J., Broderick, S., Balak, M., Chang, W.-C., Yu, C.-J., Gazdar, A., Pass, H., Rusch, V., Gerald, W., Huang, S.-F., Yang, P.-C., Miller, V., Ladanyi, M., Yang, C.-H., Pao, W. (2007). MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl. Acad. Sci. USA 104: 20932-20937 [Abstract] [Full Text]
Deng, J., Shimamura, T., Perera, S., Carlson, N. E., Cai, D., Shapiro, G. I., Wong, K.-K., Letai, A. (2007). Proapoptotic BH3-Only BCL-2 Family Protein BIM Connects Death Signaling from Epidermal Growth Factor Receptor Inhibition to the Mitochondrion. Cancer Res. 67: 11867-11875 [Abstract] [Full Text]
Engelman, J. A., Zejnullahu, K., Gale, C.-M., Lifshits, E., Gonzales, A. J., Shimamura, T., Zhao, F., Vincent, P. W., Naumov, G. N., Bradner, J. E., Althaus, I. W., Gandhi, L., Shapiro, G. I., Nelson, J. M., Heymach, J. V., Meyerson, M., Wong, K.-K., Janne, P. A. (2007). PF00299804, an Irreversible Pan-ERBB Inhibitor, Is Effective in Lung Cancer Models with EGFR and ERBB2 Mutations that Are Resistant to Gefitinib. Cancer Res. 67: 11924-11932 [Abstract] [Full Text]
Yu, Z., Boggon, T. J., Kobayashi, S., Jin, C., Ma, P. C., Dowlati, A., Kern, J. A., Tenen, D. G., Halmos, B. (2007). Resistance to an Irreversible Epidermal Growth Factor Receptor (EGFR) Inhibitor in EGFR-Mutant Lung Cancer Reveals Novel Treatment Strategies. Cancer Res. 67: 10417-10427 [Abstract] [Full Text]
Raz, T., Nardi, V., Azam, M., Cortes, J., Daley, G. Q. (2007). Farnesyl transferase inhibitor resistance probed by target mutagenesis. Blood 110: 2102-2109 [Abstract] [Full Text]
Janne, P. A., von Pawel, J., Cohen, R. B., Crino, L., Butts, C. A., Olson, S. S., Eiseman, I. A., Chiappori, A. A., Yeap, B. Y., Lenehan, P. F., Dasse, K., Sheeran, M., Bonomi, P. D. (2007). Multicenter, Randomized, Phase II Trial of CI-1033, an Irreversible Pan-ERBB Inhibitor, for Previously Treated Advanced Non Small-Cell Lung Cancer. JCO 25: 3936-3944 [Abstract] [Full Text]
Edwards, A., Li, J., Atadja, P., Bhalla, K., Haura, E. B. (2007). Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor dependent human lung cancer cells. Molecular Cancer Therapeutics 6: 2515-2524 [Abstract] [Full Text]
Riely, G. J., Kris, M. G., Zhao, B., Akhurst, T., Milton, D. T., Moore, E., Tyson, L., Pao, W., Rizvi, N. A., Schwartz, L. H., Miller, V. A. (2007). Prospective Assessment of Discontinuation and Reinitiation of Erlotinib or Gefitinib in Patients with Acquired Resistance to Erlotinib or Gefitinib Followed by the Addition of Everolimus. Clin. Cancer Res. 13: 5150-5155 [Abstract] [Full Text]
Ogino, A., Kitao, H., Hirano, S., Uchida, A., Ishiai, M., Kozuki, T., Takigawa, N., Takata, M., Kiura, K., Tanimoto, M. (2007). Emergence of Epidermal Growth Factor Receptor T790M Mutation during Chronic Exposure to Gefitinib in a Non Small Cell Lung Cancer Cell Line. Cancer Res. 67: 7807-7814 [Abstract] [Full Text]
Franovic, A., Gunaratnam, L., Smith, K., Robert, I., Patten, D., Lee, S. (2007). Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer. Proc. Natl. Acad. Sci. USA 104: 13092-13097 [Abstract] [Full Text]
Godin-Heymann, N., Bryant, I., Rivera, M. N., Ulkus, L., Bell, D. W., Riese, D. J. II, Settleman, J., Haber, D. A. (2007). Oncogenic Activity of Epidermal Growth Factor Receptor Kinase Mutant Alleles Is Enhanced by the T790M Drug Resistance Mutation. Cancer Res. 67: 7319-7326 [Abstract] [Full Text]
Nakajima, T., Yasufuku, K., Suzuki, M., Hiroshima, K., Kubo, R., Mohammed, S., Miyagi, Y., Matsukuma, S., Sekine, Y., Fujisawa, T. (2007). Assessment of Epidermal Growth Factor Receptor Mutation by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration. Chest 132: 597-602 [Abstract] [Full Text]
Wong, K.-K. (2007). HKI-272 in Non Small Cell Lung Cancer. Clin. Cancer Res. 13: 4593s-4596s [Abstract] [Full Text]
Little, S. E., Bax, D. A., Rodriguez-Pinilla, M., Natrajan, R., Messahel, B., Pritchard-Jones, K., Vujanic, G. M., Reis-Filho, J. S., Jones, C. (2007). Multifaceted Dysregulation of the Epidermal Growth Factor Receptor Pathway in Clear Cell Sarcoma of the Kidney. Clin. Cancer Res. 13: 4360-4364 [Abstract] [Full Text]
Karamouzis, M. V., Grandis, J. R., Argiris, A. (2007). Therapies Directed Against Epidermal Growth Factor Receptor in Aerodigestive Carcinomas. JAMA 298: 70-82 [Abstract] [Full Text]
Chiang, C.-T., Way, T.-D., Lin, J.-K. (2007). Sensitizing HER2-overexpressing cancer cells to luteolin-induced apoptosis through suppressing p21WAF1/CIP1 expression with rapamycin. Molecular Cancer Therapeutics 6: 2127-2138 [Abstract] [Full Text]
Gridelli, C., Bareschino, M. A., Schettino, C., Rossi, A., Maione, P., Ciardiello, F. (2007). Erlotinib in Non-Small Cell Lung Cancer Treatment: Current Status and Future Development. The Oncologist 12: 840-849 [Abstract] [Full Text]
Bunn, P. A. Jr (2007). Can Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Be Overcome by Different Small-Molecule Tyrosine Kinase Inhibitors?. JCO 25: 2504-2505 [Full Text]
Cho, B. C., Im, C.-K., Park, M.-S., Kim, S. K., Chang, J., Park, J. P., Choi, H. J., Kim, Y. J., Shin, S.-J., Sohn, J. H., Kim, H., Kim, J. H. (2007). Phase II Study of Erlotinib in Advanced Non-Small-Cell Lung Cancer After Failure of Gefitinib. JCO 25: 2528-2533 [Abstract] [Full Text]
Yamasaki, F., Johansen, M. J., Zhang, D., Krishnamurthy, S., Felix, E., Bartholomeusz, C., Aguilar, R. J., Kurisu, K., Mills, G. B., Hortobagyi, G. N., Ueno, N. T. (2007). Acquired Resistance to Erlotinib in A-431 Epidermoid Cancer Cells Requires Down-regulation of MMAC1/PTEN and Up-regulation of Phosphorylated Akt. Cancer Res. 67: 5779-5788 [Abstract] [Full Text]
Li, J., Berbeco, R., Distel, R. J., Janne, P. A., Wang, L., Makrigiorgos, G. M. (2007). s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis. Nucleic Acids Res 35: e84-e84 [Abstract] [Full Text]
Cappuzzo, F., Ligorio, C., Janne, P. A., Toschi, L., Rossi, E., Trisolini, R., Paioli, D., Holmes, A. J., Magrini, E., Finocchiaro, G., Bartolini, S., Cancellieri, A., Ciardiello, F., Patelli, M., Crino, L., Varella-Garcia, M. (2007). Prospective Study of Gefitinib in Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization-Positive/Phospho-Akt-Positive or Never Smoker Patients With Advanced Non-Small-Cell Lung Cancer: The ONCOBELL Trial. JCO 25: 2248-2255 [Abstract] [Full Text]
Horiike, A., Kimura, H., Nishio, K., Ohyanagi, F., Satoh, Y., Okumura, S., Ishikawa, Y., Nakagawa, K., Horai, T., Nishio, M. (2007). Detection of Epidermal Growth Factor Receptor Mutation in Transbronchial Needle Aspirates of Non-Small Cell Lung Cancer. Chest 131: 1628-1634 [Abstract] [Full Text]
Li, T., Ling, Y.-H., Goldman, I. D., Perez-Soler, R. (2007). Schedule-Dependent Cytotoxic Synergism of Pemetrexed and Erlotinib in Human Non-Small Cell Lung Cancer Cells. Clin. Cancer Res. 13: 3413-3422 [Abstract] [Full Text]
Toyooka, S., Date, H., Uchida, A., Kiura, K., Takata, M. (2007). The Epidermal Growth Factor Receptor D761Y Mutation and Effect of Tyrosine Kinase Inhibitor. Clin. Cancer Res. 13: 3431-3431 [Full Text]
Ray, A., Cowan-Jacob, S. W., Manley, P. W., Mestan, J., Griffin, J. D. (2007). Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study. Blood 109: 5011-5015 [Abstract] [Full Text]
Vikis, H., Sato, M., James, M., Wang, D., Wang, Y., Wang, M., Jia, D., Liu, Y., Bailey-Wilson, J. E., Amos, C. I., Pinney, S. M., Petersen, G. M., de Andrade, M., Yang, P., Wiest, J. S., Fain, P. R., Schwartz, A. G., Gazdar, A., Gaba, C., Rothschild, H., Mandal, D., Kupert, E., Seminara, D., Viswanathan, A., Govindan, R., Minna, J., Anderson, M. W., You, M. (2007). EGFR-T790M Is a Rare Lung Cancer Susceptibility Allele with Enhanced Kinase Activity. Cancer Res. 67: 4665-4670 [Abstract] [Full Text]
Greshock, J., Nathanson, K., Martin, A.-M., Zhang, L., Coukos, G., Weber, B. L., Zaks, T. Z. (2007). Cancer Cell Lines as Genetic Models of Their Parent Histology: Analyses Based on Array Comparative Genomic Hybridization. Cancer Res. 67: 3594-3600 [Abstract] [Full Text]
Hirsch, F., Varella-Garcia, M, Cappuzzo, F, McCoy, J, Bemis, L, Xavier, A., Dziadziuszko, R, Gumerlock, P, Chansky, K, West, H, Gazdar, A., Crino, L, Gandara, D., Franklin, W., Bunn, P. Jr (2007). Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Ann Oncol 18: 752-760 [Abstract] [Full Text]
Fridman, J. S., Caulder, E., Hansbury, M., Liu, X., Yang, G., Wang, Q., Lo, Y., Zhou, B.-B., Pan, M., Thomas, S. M., Grandis, J. R., Zhuo, J., Yao, W., Newton, R. C., Friedman, S. M., Scherle, P. A., Vaddi, K. (2007). Selective Inhibition of ADAM Metalloproteases as a Novel Approach for Modulating ErbB Pathways in Cancer. Clin. Cancer Res. 13: 1892-1902 [Abstract] [Full Text]
Mulloy, R., Ferrand, A., Kim, Y., Sordella, R., Bell, D. W., Haber, D. A., Anderson, K. S., Settleman, J. (2007). Epidermal Growth Factor Receptor Mutants from Human Lung Cancers Exhibit Enhanced Catalytic Activity and Increased Sensitivity to Gefitinib. Cancer Res. 67: 2325-2330 [Abstract] [Full Text]
Tabernero, J. (2007). The Role of VEGF and EGFR Inhibition: Implications for Combining Anti-VEGF and Anti-EGFR Agents. Mol Cancer Res 5: 203-220 [Abstract] [Full Text]
Steiner, P., Joynes, C., Bassi, R., Wang, S., Tonra, J. R., Hadari, Y. R., Hicklin, D. J. (2007). 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. 13: 1540-1551 [Abstract] [Full Text]
Zhang, X., Chang, A. (2007). Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer. J. Med. Genet. 44: 166-172 [Abstract] [Full Text]
Sequist, L. V. (2007). Second-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. The Oncologist 12: 325-330 [Abstract] [Full Text]
Subramanian, J., Govindan, R. (2007). Lung Cancer in Never Smokers: A Review. JCO 25: 561-570 [Abstract] [Full Text]
Sequist, L. V., Bell, D. W., Lynch, T. J., Haber, D. A. (2007). Molecular Predictors of Response to Epidermal Growth Factor Receptor Antagonists in Non-Small-Cell Lung Cancer. JCO 25: 587-595 [Abstract] [Full Text]
Karamouzis, M. V., Konstantinopoulos, P. A., Papavassiliou, A. G. (2007). The Activator Protein-1 Transcription Factor in Respiratory Epithelium Carcinogenesis. Mol Cancer Res 5: 109-120 [Abstract] [Full Text]
Wu, W., Onn, A., Isobe, T., Itasaka, S., Langley, R. R., Shitani, T., Shibuya, K., Komaki, R., Ryan, A. J., Fidler, I. J., Herbst, R. S., O'Reilly, M. S. (2007). Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade. Molecular Cancer Therapeutics 6: 471-483 [Abstract] [Full Text]
Schiffer, H. H., Reding, E. C., Fuhs, S. R., Lu, Q., Piu, F., Wong, S., Littler, P.-L. H., Weiner, D. M., Keefe, W., Tan, P. K., Nash, N. R., Knapp, A. E., Olsson, R., Brann, M. R. (2007). Pharmacology and Signaling Properties of Epidermal Growth Factor Receptor Isoforms Studied by Bioluminescence Resonance Energy Transfer. Mol. Pharmacol. 71: 508-518 [Abstract] [Full Text]
Toschi, L., Cappuzzo, F. (2007). Understanding the New Genetics of Responsiveness to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. The Oncologist 12: 211-220 [Abstract] [Full Text]
Mellinghoff, I. K., Cloughesy, T. F., Mischel, P. S. (2007). PTEN-Mediated Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors. Clin. Cancer Res. 13: 378-381 [Abstract] [Full Text]
Chin, T. M., Anuar, D., Soo, R., Salto-Tellez, M., Li, W. Q., Ahmad, B., Lee, S. C., Goh, B. C., Kawakami, K., Segal, A., Iacopetta, B., Soong, R. (2007). Detection of Epidermal Growth Factor Receptor Variations by Partially Denaturing HPLC. Clin. Chem. 53: 62-70 [Abstract] [Full Text]
Sequist, L. V., Joshi, V. A., Janne, P. A., Muzikansky, A., Fidias, P., Meyerson, M., Haber, D. A., Kucherlapati, R., Johnson, B. E., Lynch, T. J. (2007). Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing.. The Oncologist 12: 90-98 [Abstract] [Full Text]
Perez-Torres, M., Guix, M., Gonzalez, A., Arteaga, C. L. (2006). Epidermal Growth Factor Receptor (EGFR) Antibody Down-regulates Mutant Receptors and Inhibits Tumors Expressing EGFR Mutations. J. Biol. Chem. 281: 40183-40192 [Abstract] [Full Text]
Skaggs, B. J., Gorre, M. E., Ryvkin, A., Burgess, M. R., Xie, Y., Han, Y., Komisopoulou, E., Brown, L. M., Loo, J. A., Landaw, E. M., Sawyers, C. L., Graeber, T. G. (2006). Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants. Proc. Natl. Acad. Sci. USA 103: 19466-19471 [Abstract] [Full Text]
Rosell, R., Taron, M., Reguart, N., Isla, D., Moran, T. (2006). Epidermal Growth Factor Receptor Activation: How Exon 19 and 21 Mutations Changed Our Understanding of the Pathway. Clin. Cancer Res. 12: 7222-7231 [Abstract] [Full Text]
Riely, G. J., Politi, K. A., Miller, V. A., Pao, W. (2006). Update on Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer. Clin. Cancer Res. 12: 7232-7241 [Abstract] [Full Text]
Kobayashi, S., Shimamura, T., Monti, S., Steidl, U., Hetherington, C. J., Lowell, A. M., Golub, T., Meyerson, M., Tenen, D. G., Shapiro, G. I., Halmos, B. (2006). Transcriptional Profiling Identifies Cyclin D1 as a Critical Downstream Effector of Mutant Epidermal Growth Factor Receptor Signaling. Cancer Res. 66: 11389-11398 [Abstract] [Full Text]
Balak, M. N., Gong, Y., Riely, G. J., Somwar, R., Li, A. R., Zakowski, M. F., Chiang, A., Yang, G., Ouerfelli, O., Kris, M. G., Ladanyi, M., Miller, V. A., Pao, W. (2006). Novel D761Y and Common Secondary T790M Mutations in Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinomas with Acquired Resistance to Kinase Inhibitors.. Clin. Cancer Res. 12: 6494-6501 [Abstract] [Full Text]
Milton, D. T., Riely, G. J., Pao, W., Miller, V. A., Kris, M. G., Heelan, R. T. (2006). Molecular On/Off Switch. JCO 24: 4940-4942 [Full Text]
Giaccone, G., Gallegos Ruiz, M., Le Chevalier, T., Thatcher, N., Smit, E., Rodriguez, J. A., Janne, P., Oulid-Aissa, D., Soria, J.-C. (2006). Erlotinib for Frontline Treatment of Advanced Non-Small Cell Lung Cancer: a Phase II Study.. Clin. Cancer Res. 12: 6049-6055 [Abstract] [Full Text]
Das, A. K., Sato, M., Story, M. D., Peyton, M., Graves, R., Redpath, S., Girard, L., Gazdar, A. F., Shay, J. W., Minna, J. D., Nirodi, C. S. (2006). Non-Small Cell Lung Cancers with Kinase Domain Mutations in the Epidermal Growth Factor Receptor Are Sensitive to Ionizing Radiation. Cancer Res. 66: 9601-9608 [Abstract] [Full Text]
Krueger, K. E., Srivastava, S. (2006). Posttranslational Protein Modifications: Current Implications for Cancer Detection, Prevention, and Therapeutics. Mol. Cell. Proteomics 5: 1799-1810 [Full Text]
Kosaka, T., Yatabe, Y., Endoh, H., Yoshida, K., Hida, T., Tsuboi, M., Tada, H., Kuwano, H., Mitsudomi, T. (2006). Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib.. Clin. Cancer Res. 12: 5764-5769 [Abstract] [Full Text]
Amicarelli, G., Adlerstein, D., Shehi, E., Wang, F., Makrigiorgos, G. M. (2006). Genotype-Specific Signal Generation Based on Digestion of 3-Way DNA Junctions: Application to KRAS Variation Detection. Clin. Chem. 52: 1855-1863 [Abstract] [Full Text]
Jackman, D. M., Holmes, A. J., Lindeman, N., Wen, P. Y., Kesari, S., Borras, A. M., Bailey, C., de Jong, F., Janne, P. A., Johnson, B. E. (2006). Response and Resistance in a Non-Small-Cell Lung Cancer Patient With an Epidermal Growth Factor Receptor Mutation and Leptomeningeal Metastases Treated With High-Dose Gefitinib. JCO 24: 4517-4520 [Full Text]
Inukai, M., Toyooka, S., Ito, S., Asano, H., Ichihara, S., Soh, J., Suehisa, H., Ouchida, M., Aoe, K., Aoe, M., Kiura, K., Shimizu, N., Date, H. (2006). Presence of Epidermal Growth Factor Receptor Gene T790M Mutation as a Minor Clone in Non-Small Cell Lung Cancer. Cancer Res. 66: 7854-7858 [Abstract] [Full Text]
von Bubnoff, N., Manley, P. W., Mestan, J., Sanger, J., Peschel, C., Duyster, J. (2006). Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107). Blood 108: 1328-1333 [Abstract] [Full Text]
Chou, W.-C., Huang, S.-F., Yeh, K.-Y., Wang, H.-M., Liu, M.-Y., Hsieh, J.-J., Cheung, Y.-C., Chang, J. W.-C. (2006). Different Responses to Gefitinib in Lung Adenocarcinoma Coexpressing Mutant- and Wild-Type Epidermal Growth Factor Receptor Genes. Jpn J Clin Oncol 36: 523-526 [Abstract] [Full Text]
Coldren, C. D., Helfrich, B. A., Witta, S. E., Sugita, M., Lapadat, R., Zeng, C., Baron, A., Franklin, W. A., Hirsch, F. R., Geraci, M. W., Bunn, P. A. Jr. (2006). Baseline Gene Expression Predicts Sensitivity to Gefitinib in Non-Small Cell Lung Cancer Cell Lines. Mol Cancer Res 4: 521-528 [Abstract] [Full Text]
Janne, P. A. (2006). Gefitinib for Epidermal Growth Factor Receptor Mutant Lung Cancers: Searching for a Weapon of Mass Destruction. JCO 24: 3319-3321 [Full Text]
Kwak, E. L., Jankowski, J., Thayer, S. P., Lauwers, G. Y., Brannigan, B. W., Harris, P. L., Okimoto, R. A., Haserlat, S. M., Driscoll, D. R., Ferry, D., Muir, B., Settleman, J., Fuchs, C. S., Kulke, M. H., Ryan, D. P., Clark, J. W., Sgroi, D. C., Haber, D. A., Bell, D. W. (2006). Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas.. Clin. Cancer Res. 12: 4283-4287 [Abstract] [Full Text]
Engelman, J. A., Cantley, L. C. (2006). The Role of the ErbB Family Members in Non-Small Cell "Lung Cancers Sensitive to Epidermal Growth Factor Receptor Kinase Inhibitors".. Clin. Cancer Res. 12: 4372s-4376s [Abstract] [Full Text]
Thomas, R. K., Weir, B., Meyerson, M. (2006). Genomic approaches to lung cancer.. Clin. Cancer Res. 12: 4384s-4391s [Abstract] [Full Text]
Sequist, L. V., Joshi, V. A., Janne, P. A., Bell, D. W., Fidias, P., Lindeman, N. I., Louis, D. N., Lee, J. C., Mark, E. J., Longtine, J., Verlander, P., Kucherlapati, R., Meyerson, M., Haber, D. A., Johnson, B. E., Lynch, T. J. (2006). Epidermal growth factor receptor mutation testing in the care of lung cancer patients.. Clin. Cancer Res. 12: 4403s-4408s [Abstract] [Full Text]

Comments and questions? Please contact us.