Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib
Thomas J. Lynch, M.D., Daphne W. Bell, Ph.D., Raffaella Sordella, Ph.D., Sarada Gurubhagavatula, M.D., Ross A. Okimoto, B.S., Brian W. Brannigan, B.A., Patricia L. Harris, M.S., Sara M. Haserlat, B.A., Jeffrey G. Supko, Ph.D., Frank G. Haluska, M.D., Ph.D., David N. Louis, M.D., David C. Christiani, M.D., Jeff Settleman, Ph.D., and Daniel A. Haber, M.D., Ph.D.
Background Most patients with non–small-cell lung cancerhave no response to the tyrosine kinase inhibitor gefitinib,which targets the epidermal growth factor receptor (EGFR). However,about 10 percent of patients have a rapid and often dramaticclinical response. The molecular mechanisms underlying sensitivityto gefitinib are unknown.
Methods We searched for mutations in the EGFR gene in primarytumors from patients with non–small-cell lung cancer whohad a response to gefitinib, those who did not have a response,and those who had not been exposed to gefitinib. The functionalconsequences of identified mutations were evaluated after themutant proteins were expressed in cultured cells.
Results Somatic mutations were identified in the tyrosine kinasedomain of the EGFR gene in eight of nine patients with gefitinib-responsivelung cancer, as compared with none of the seven patients withno response (P<0.001). Mutations were either small, in-framedeletions or amino acid substitutions clustered around the ATP-bindingpocket of the tyrosine kinase domain. Similar mutations weredetected in tumors from 2 of 25 patients with primary non–small-celllung cancer who had not been exposed to gefitinib (8 percent).All mutations were heterozygous, and identical mutations wereobserved in multiple patients, suggesting an additive specificgain of function. In vitro, EGFR mutants demonstrated enhancedtyrosine kinase activity in response to epidermal growth factorand increased sensitivity to inhibition by gefitinib.
Conclusions A subgroup of patients with non–small-celllung cancer have specific mutations in the EGFR gene, whichcorrelate with clinical responsiveness to the tyrosine kinaseinhibitor gefitinib. These mutations lead to increased growthfactor signaling and confer susceptibility to the inhibitor.Screening for such mutations in lung cancers may identify patientswho will have a response to gefitinib.
Source Information
From the Cancer Center (T.J.L., D.W.B., R.S., S.G., R.A.O., B.W.B., P.L.H., S.M.H., J.G.S., F.G.H., D.N.L., D.C.C., J.S., D.A.H.) and the Departments of Medicine (T.J.L., D.W.B., J.G.S., F.G.H., D.C.C., J.S., D.A.H.) and Pathology (D.N.L.), Massachusetts General Hospital and Harvard Medical School; and the Harvard School of Public Health (S.G., D.C.C.) — all in Boston. Drs. Lynch, Bell, and Sordella contributed equally to the article. This article was published at www.nejm.org on April 29, 2004.
Address reprint requests to Dr. Haber at MGH Cancer Center, Bldg. 149, 13th St., Charlestown, MA 02129, or at haber{at}helix.mgh.harvard.edu.
EGFR Mutations and Sensitivity to Gefitinib
Sorscher S. M., Rich J. N., Rasheed B.K. A., Yan H., Rossi G., Marchioni A., Longo L., Haber D. A., Bell D. W., Lynch T. J.
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N Engl J Med 2004;
351:1260-1261, Sep 16, 2004.
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[Abstract][Full Text]
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[Abstract][Full Text]
Pernas, F. G., Allen, C. T., Winters, M. E., Yan, B., Friedman, J., Dabir, B., Saigal, K., Mundinger, G. S., Xu, X., Morris, J. C., Calvo, K. R., Van Waes, C., Chen, Z.
(2009). Proteomic Signatures of Epidermal Growth Factor Receptor and Survival Signal Pathways Correspond to Gefitinib Sensitivity in Head and Neck Cancer. Clin. Cancer Res.
15: 2361-2372
[Abstract][Full Text]
Inoue, A., Kobayashi, K., Usui, K., Maemondo, M., Okinaga, S., Mikami, I., Ando, M., Yamazaki, K., Saijo, Y., Gemma, A., Miyazawa, H., Tanaka, T., Ikebuchi, K., Nukiwa, T., Morita, S., Hagiwara, K.
(2009). First-Line Gefitinib for Patients With Advanced Non-Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations Without Indication for Chemotherapy. JCO
27: 1394-1400
[Abstract][Full Text]
Pratilas, C. A., Taylor, B. S., Ye, Q., Viale, A., Sander, C., Solit, D. B., Rosen, N.
(2009). V600EBRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc. Natl. Acad. Sci. USA
106: 4519-4524
[Abstract][Full Text]
Nikolova, D. A., Asangani, I. A., Nelson, L. D., Hughes, D. P.M., Siwak, D. R., Mills, G. B., Harms, A., Buchholz, E., Pilz, L. R., Manegold, C., Allgayer, H.
(2009). Cetuximab Attenuates Metastasis and u-PAR Expression in Non-Small Cell Lung Cancer: u-PAR and E-Cadherin are Novel Biomarkers of Cetuximab Sensitivity. Cancer Res.
69: 2461-2470
[Abstract][Full Text]
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(2009). Single-Molecule Detection of Epidermal Growth Factor Receptor Mutations in Plasma by Microfluidics Digital PCR in Non-Small Cell Lung Cancer Patients. Clin. Cancer Res.
15: 2076-2084
[Abstract][Full Text]
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(2009). Randomized Phase II Trial of Erlotinib Versus Temozolomide or Carmustine in Recurrent Glioblastoma: EORTC Brain Tumor Group Study 26034. JCO
27: 1268-1274
[Abstract][Full Text]
Al-Nedawi, K., Meehan, B., Kerbel, R. S., Allison, A. C., Rak, J.
(2009). Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc. Natl. Acad. Sci. USA
106: 3794-3799
[Abstract][Full Text]
Jiang, H.
(2009). Overview of Gefitinib in Non-small Cell Lung Cancer: An Asian Perspective. Jpn J Clin Oncol
39: 137-150
[Abstract][Full Text]
Tvorogov, D., Sundvall, M., Kurppa, K., Hollmen, M., Repo, S., Johnson, M. S., Elenius, K.
(2009). Somatic Mutations of ErbB4: SELECTIVE LOSS-OF-FUNCTION PHENOTYPE AFFECTING SIGNAL TRANSDUCTION PATHWAYS IN CANCER. J. Biol. Chem.
284: 5582-5591
[Abstract][Full Text]
Schnidar, H., Eberl, M., Klingler, S., Mangelberger, D., Kasper, M., Hauser-Kronberger, C., Regl, G., Kroismayr, R., Moriggl, R., Sibilia, M., Aberger, F.
(2009). Epidermal Growth Factor Receptor Signaling Synergizes with Hedgehog/GLI in Oncogenic Transformation via Activation of the MEK/ERK/JUN Pathway. Cancer Res.
69: 1284-1292
[Abstract][Full Text]
Nakanishi, H., Matsumoto, S., Iwakawa, R., Kohno, T., Suzuki, K., Tsuta, K., Matsuno, Y., Noguchi, M., Shimizu, E., Yokota, J.
(2009). Whole Genome Comparison of Allelic Imbalance between Noninvasive and Invasive Small-Sized Lung Adenocarcinomas. Cancer Res.
69: 1615-1623
[Abstract][Full Text]
Hait, W. N., Hambley, T. W.
(2009). Targeted Cancer Therapeutics. Cancer Res.
69: 1263-1267
[Abstract][Full Text]
Laurent-Puig, P., Lievre, A., Blons, H.
(2009). Mutations and Response to Epidermal Growth Factor Receptor Inhibitors. Clin. Cancer Res.
15: 1133-1139
[Abstract][Full Text]
Ruppert, A-M., Beau-Faller, M., Neuville, A., Guerin, E., Voegeli, A-C., Mennecier, B., Legrain, M., Molard, A., Jeung, M-Y., Gaub, M-P., Oudet, P., Quoix, E.
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20: 213-226
[Abstract][Full Text]
Memon, A. A., Jakobsen, S., Dagnaes-Hansen, F., Sorensen, B. S., Keiding, S., Nexo, E.
(2009). Positron Emission Tomography (PET) Imaging with [11C]-Labeled Erlotinib: A Micro-PET Study on Mice with Lung Tumor Xenografts. Cancer Res.
69: 873-878
[Abstract][Full Text]
Kesarwala, A. H., Samrakandi, M. M., Piwnica-Worms, D.
(2009). Proteasome Inhibition Blocks Ligand-Induced Dynamic Processing and Internalization of Epidermal Growth Factor Receptor via Altered Receptor Ubiquitination and Phosphorylation. Cancer Res.
69: 976-983
[Abstract][Full Text]
Okabe, T., Okamoto, I., Tsukioka, S., Uchida, J., Hatashita, E., Yamada, Y., Yoshida, T., Nishio, K., Fukuoka, M., Janne, P. A., Nakagawa, K.
(2009). Addition of S-1 to the Epidermal Growth Factor Receptor Inhibitor Gefitinib Overcomes Gefitinib Resistance in Non-small cell Lung Cancer Cell Lines with MET Amplification. Clin. Cancer Res.
15: 907-913
[Abstract][Full Text]
Arnes, J B, Begin, L R, Stefansson, I, Brunet, J-S, Nielsen, T O, Foulkes, W D, Akslen, L A
(2009). Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer. J. Clin. Pathol.
62: 139-146
[Abstract][Full Text]
Martelli, M. P., Sozzi, G., Hernandez, L., Pettirossi, V., Navarro, A., Conte, D., Gasparini, P., Perrone, F., Modena, P., Pastorino, U., Carbone, A., Fabbri, A., Sidoni, A., Nakamura, S., Gambacorta, M., Fernandez, P. L., Ramirez, J., Chan, J. K.C., Grigioni, W. F., Campo, E., Pileri, S. A., Falini, B.
(2009). EML4-ALK Rearrangement in Non-Small Cell Lung Cancer and Non-Tumor Lung Tissues. Am. J. Pathol.
174: 661-670
[Abstract][Full Text]
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(2009). Effect of Lapatinib on the Development of Estrogen Receptor-Negative Mammary Tumors in Mice. JNCI J Natl Cancer Inst
101: 107-113
[Abstract][Full Text]
Nose, N., Sugio, K., Oyama, T., Nozoe, T., Uramoto, H., Iwata, T., Onitsuka, T., Yasumoto, K.
(2009). Association Between Estrogen Receptor-{beta} Expression and Epidermal Growth Factor Receptor Mutation in the Postoperative Prognosis of Adenocarcinoma of the Lung. JCO
27: 411-417
[Abstract][Full Text]
Kancha, R. K., von Bubnoff, N., Peschel, C., Duyster, J.
(2009). Functional Analysis of Epidermal Growth Factor Receptor (EGFR) Mutations and Potential Implications for EGFR Targeted Therapy. Clin. Cancer Res.
15: 460-467
[Abstract][Full Text]
Broniscer, A., Baker, S. J., Stewart, C. F., Merchant, T. E., Laningham, F. H., Schaiquevich, P., Kocak, M., Morris, E. B., Endersby, R., Ellison, D. W., Gajjar, A.
(2009). Phase I and Pharmacokinetic Studies of Erlotinib Administered Concurrently with Radiotherapy for Children, Adolescents, and Young Adults with High-Grade Glioma. Clin. Cancer Res.
15: 701-707
[Abstract][Full Text]
Riely, G. J., Rizvi, N. A., Kris, M. G., Milton, D. T., Solit, D. B., Rosen, N., Senturk, E., Azzoli, C. G., Brahmer, J. R., Sirotnak, F. M., Seshan, V. E., Fogle, M., Ginsberg, M., Miller, V. A., Rudin, C. M.
(2009). Randomized Phase II Study of Pulse Erlotinib Before or After Carboplatin and Paclitaxel in Current or Former Smokers With Advanced Non-Small-Cell Lung Cancer. JCO
27: 264-270
[Abstract][Full Text]
Lutschg, J. H., Herbst, R. S., Heymach, J. V., Lippman, S. M.
(2009). Lung Cancer. NEJM
360: 87-88
[Full Text]
Gottlin, E. B., Xiangrong Guan, , Pegram, C., Cannedy, A., Campa, M. J., Patz, E. F. Jr.
(2009). Isolation of Novel EGFR-Specific VHH Domains. J Biomol Screen
14: 77-85
[Abstract]
Foster, J. M., Gatalica, Z., Lilleberg, S., Haynatzki, G., Loggie, B. W.
(2009). Novel and Existing Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor are Predictors of Optimal Resectability in Malignant Peritoneal Mesothelioma. Ann. Surg. Oncol.
16: 152-158
[Abstract][Full Text]
Huang, F., Greer, A., Hurlburt, W., Han, X., Hafezi, R., Wittenberg, G. M., Reeves, K., Chen, J., Robinson, D., Li, A., Lee, F. Y., Gottardis, M. M., Clark, E., Helman, L., Attar, R. M., Dongre, A., Carboni, J. M.
(2009). The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors. Cancer Res.
69: 161-170
[Abstract][Full Text]
Card, A., Caldwell, C., Min, H., Lokchander, B., Hualin Xi, , Sciabola, S., Kamath, A. V., Clugston, S. L., Tschantz, W. R., Leyu Wang, , Moshinsky, D. J.
(2009). High-Throughput Biochemical Kinase Selectivity Assays: Panel Development and Screening Applications. J Biomol Screen
14: 31-42
[Abstract]
Ma, W., Kantarjian, H., Zhang, X., Yeh, C.-H., Zhang, Z. J., Verstovsek, S., Albitar, M.
(2009). Mutation Profile of JAK2 Transcripts in Patients with Chronic Myeloproliferative Neoplasias. J. Mol. Diagn.
11: 49-53
[Abstract][Full Text]
Marek, L., Ware, K. E., Fritzsche, A., Hercule, P., Helton, W. R., Smith, J. E., McDermott, L. A., Coldren, C. D., Nemenoff, R. A., Merrick, D. T., Helfrich, B. A., Bunn, P. A. Jr., Heasley, L. E.
(2009). Fibroblast Growth Factor (FGF) and FGF Receptor-Mediated Autocrine Signaling in Non-Small-Cell Lung Cancer Cells. Mol. Pharmacol.
75: 196-207
[Abstract][Full Text]
Socinski, M. A.
(2009). What Guides Decisions about the Use of Epidermal Growth Factor Receptor Antibody or Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Advanced Non-small Cell Lung Cancer?. Am Soc Clin Oncol Ed Book
2009: 436-443
[Abstract][Full Text]
Di Nicolantonio, F., Arena, S., Gallicchio, M., Zecchin, D., Martini, M., Flonta, S. E., Stella, G. M., Lamba, S., Cancelliere, C., Russo, M., Geuna, M., Appendino, G., Fantozzi, R., Medico, E., Bardelli, A.
(2008). Replacement of normal with mutant alleles in the genome of normal human cells unveils mutation-specific drug responses. Proc. Natl. Acad. Sci. USA
105: 20864-20869
[Abstract][Full Text]
Luo, B., Cheung, H. W., Subramanian, A., Sharifnia, T., Okamoto, M., Yang, X., Hinkle, G., Boehm, J. S., Beroukhim, R., Weir, B. A., Mermel, C., Barbie, D. A., Awad, T., Zhou, X., Nguyen, T., Piqani, B., Li, C., Golub, T. R., Meyerson, M., Hacohen, N., Hahn, W. C., Lander, E. S., Sabatini, D. M., Root, D. E.
(2008). Highly parallel identification of essential genes in cancer cells. Proc. Natl. Acad. Sci. USA
105: 20380-20385
[Abstract][Full Text]
Kim, H.-T., Lee, J.-E., Shin, E.-S., Yoo, Y.-K., Cho, J.-H., Yun, M.-H., Kim, Y.-H., Kim, S.-K., Kim, H.-J., Jang, T.-W., Kwak, S.-M., Kim, C.-S., Ryu, J.-S.
(2008). Effect of BRCA1 Haplotype on Survival of Non-Small-Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy. JCO
26: 5972-5979
[Abstract][Full Text]
Soda, M., Takada, S., Takeuchi, K., Choi, Y. L., Enomoto, M., Ueno, T., Haruta, H., Hamada, T., Yamashita, Y., Ishikawa, Y., Sugiyama, Y., Mano, H.
(2008). A mouse model for EML4-ALK-positive lung cancer. Proc. Natl. Acad. Sci. USA
105: 19893-19897
[Abstract][Full Text]
Takano, T., Fukui, T., Ohe, Y., Tsuta, K., Yamamoto, S., Nokihara, H., Yamamoto, N., Sekine, I., Kunitoh, H., Furuta, K., Tamura, T.
(2008). EGFR Mutations Predict Survival Benefit From Gefitinib in Patients With Advanced Lung Adenocarcinoma: A Historical Comparison of Patients Treated Before and After Gefitinib Approval in Japan. JCO
26: 5589-5595
[Abstract][Full Text]
Lam, E. T., O'Bryant, C. L., Basche, M., Gustafson, D. L., Serkova, N., Baron, A., Holden, S. N., Dancey, J., Eckhardt, S. G., Gore, L.
(2008). A phase I study of gefitinib, capecitabine, and celecoxib in patients with advanced solid tumors. Molecular Cancer Therapeutics
7: 3685-3694
[Abstract][Full Text]
Press, M. F., Finn, R. S., Cameron, D., Di Leo, A., Geyer, C. E., Villalobos, I. E., Santiago, A., Guzman, R., Gasparyan, A., Ma, Y., Danenberg, K., Martin, A. M., Williams, L., Oliva, C., Stein, S., Gagnon, R., Arbushites, M., Koehler, M. T.
(2008). HER-2 Gene Amplification, HER-2 and Epidermal Growth Factor Receptor mRNA and Protein Expression, and Lapatinib Efficacy in Women with Metastatic Breast Cancer. Clin. Cancer Res.
14: 7861-7870
[Abstract][Full Text]
Dickler, M. N., Rugo, H. S., Eberle, C. A., Brogi, E., Caravelli, J. F., Panageas, K. S., Boyd, J., Yeh, B., Lake, D. E., Dang, C. T., Gilewski, T. A., Bromberg, J. F., Seidman, A. D., D'Andrea, G. M., Moasser, M. M., Melisko, M., Park, J. W., Dancey, J., Norton, L., Hudis, C. A.
(2008). A Phase II Trial of Erlotinib in Combination with Bevacizumab in Patients with Metastatic Breast Cancer. Clin. Cancer Res.
14: 7878-7883
[Abstract][Full Text]
Wu, S.-G., Chang, Y.-L., Hsu, Y.-C., Wu, J.-Y., Yang, C.-H., Yu, C.-J., Tsai, M.-F., Shih, J.-Y., Yang, P.-C.
(2008). Good Response to Gefitinib in Lung Adenocarcinoma of Complex Epidermal Growth Factor Receptor (EGFR) Mutations with the Classical Mutation Pattern. The Oncologist
13: 1276-1284
[Abstract][Full Text]
Pratilas, C. A., Hanrahan, A. J., Halilovic, E., Persaud, Y., Soh, J., Chitale, D., Shigematsu, H., Yamamoto, H., Sawai, A., Janakiraman, M., Taylor, B. S., Pao, W., Toyooka, S., Ladanyi, M., Gazdar, A., Rosen, N., Solit, D. B.
(2008). Genetic Predictors of MEK Dependence in Non-Small Cell Lung Cancer. Cancer Res.
68: 9375-9383
[Abstract][Full Text]
Yano, S., Wang, W., Li, Q., Matsumoto, K., Sakurama, H., Nakamura, T., Ogino, H., Kakiuchi, S., Hanibuchi, M., Nishioka, Y., Uehara, H., Mitsudomi, T., Yatabe, Y., Nakamura, T., Sone, S.
(2008). Hepatocyte Growth Factor Induces Gefitinib Resistance of Lung Adenocarcinoma with Epidermal Growth Factor Receptor-Activating Mutations. Cancer Res.
68: 9479-9487
[Abstract][Full Text]
Sohn, H.-J., Yang, Y.-J., Ryu, J.-S., Oh, S. J., Im, K. C., Moon, D. H., Lee, D. H., Suh, C., Lee, J.-S., Kim, S.-W.
(2008). [18F]Fluorothymidine Positron Emission Tomography before and 7 Days after Gefitinib Treatment Predicts Response in Patients with Advanced Adenocarcinoma of the Lung. Clin. Cancer Res.
14: 7423-7429
[Abstract][Full Text]
Bean, J., Riely, G. J., Balak, M., Marks, J. L., Ladanyi, M., Miller, V. A., Pao, W.
(2008). Acquired Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors Associated with a Novel T854A Mutation in a Patient with EGFR-Mutant Lung Adenocarcinoma. Clin. Cancer Res.
14: 7519-7525
[Abstract][Full Text]
Anglesio, M. S., Arnold, J. M., George, J., Tinker, A. V., Tothill, R., Waddell, N., Simms, L., Locandro, B., Fereday, S., Traficante, N., Russell, P., Sharma, R., Birrer, M. J., AOCS Study Group, , deFazio, A., Chenevix-Trench, G., Bowtell, D. D.L.
(2008). Mutation of ERBB2 Provides a Novel Alternative Mechanism for the Ubiquitous Activation of RAS-MAPK in Ovarian Serous Low Malignant Potential Tumors. Mol Cancer Res
6: 1678-1690
[Abstract][Full Text]
Ko, J.-C., Hong, J.-H., Wang, L.-H., Cheng, C.-M., Ciou, S.-C., Lin, S.-T., Jheng, M.-Y., Lin, Y.-W.
(2008). Role of repair protein Rad51 in regulating the response to gefitinib in human non-small cell lung cancer cells. Molecular Cancer Therapeutics
7: 3632-3641
[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
19: 1903-1909
[Abstract][Full Text]
Chin, T. M., Quinlan, M. P., Singh, A., Sequist, L. V., Lynch, T. J., Haber, D. A., Sharma, S. V., Settleman, J.
(2008). Reduced Erlotinib Sensitivity of Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer following Cisplatin Exposure: A Cell Culture Model of Second-line Erlotinib Treatment. Clin. Cancer Res.
14: 6867-6876
[Abstract][Full Text]
Yonesaka, K., Zejnullahu, K., Lindeman, N., Homes, A. J., Jackman, D. M., Zhao, F., Rogers, A. M., Johnson, B. E., Janne, P. A.
(2008). Autocrine Production of Amphiregulin Predicts Sensitivity to Both Gefitinib and Cetuximab in EGFR Wild-type Cancers. Clin. Cancer Res.
14: 6963-6973
[Abstract][Full Text]
Costa, D. B., Nguyen, K.-S. H., Cho, B. C., Sequist, L. V., Jackman, D. M., Riely, G. J., Yeap, B. Y., Halmos, B., Kim, J. H., Janne, P. A., Huberman, M. S., Pao, W., Tenen, D. G., Kobayashi, S.
(2008). Effects of Erlotinib in EGFR Mutated Non-Small Cell Lung Cancers with Resistance to Gefitinib. Clin. Cancer Res.
14: 7060-7067
[Abstract][Full Text]
Herbst, R. S., Sandler, A.
(2008). Bevacizumab and Erlotinib: A Promising New Approach to the Treatment of Advanced NSCLC. The Oncologist
13: 1166-1176
[Abstract][Full Text]
Janne, P. A.
(2008). Gefitinib First or Gefitinib Second: Is Timing Everything in the Treatment of EGFR Mutant Non-Small Cell Lung Cancer?. Am. J. Respir. Crit. Care Med.
178: 783-785
[Full Text]
Wu, J.-Y., Yu, C.-J., Yang, C.-H., Wu, S.-G., Chiu, Y.-H., Gow, C.-H., Chang, Y.-C., Hsu, Y.-C., Wei, P.-F., Shih, J.-Y., Yang, P.-C.
(2008). First- or Second-line Therapy with Gefitinib Produces Equal Survival in Non-Small Cell Lung Cancer. Am. J. Respir. Crit. Care Med.
178: 847-853
[Abstract][Full Text]
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