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.
Taube, S. E., Clark, G. M., Dancey, J. E., McShane, L. M., Sigman, C. C., Gutman, S. I.
(2009). A Perspective on Challenges and Issues in Biomarker Development and Drug and Biomarker Codevelopment. JNCI J Natl Cancer Inst
101: 1453-1463
[Abstract][Full Text]
Peled, N., Yoshida, K., Wynes, M. W., Hirsch, F. R.
(2009). Review: Predictive and prognostic markers for epidermal growth factor receptor inhibitor therapy in non-small cell lung cancer. Therapeutic Advances in Medical Oncology
1: 137-144
[Abstract]
Green, M. D., Francis, P. A., Gebski, V., Harvey, V., Karapetis, C., Chan, A., Snyder, R., Fong, A., Basser, R., Forbes, J. F., on behalf of the Australian New Zealand Breast Can,
(2009). Gefitinib treatment in hormone-resistant and hormone receptor-negative advanced breast cancer. Ann Oncol
20: 1813-1817
[Abstract][Full Text]
Sholl, L. M., Yeap, B. Y., Iafrate, A. J., Holmes-Tisch, A. J., Chou, Y.-P., Wu, M.-T., Goan, Y.-G., Su, L., Benedettini, E., Yu, J., Loda, M., Janne, P. A., Christiani, D. C., Chirieac, L. R.
(2009). Lung Adenocarcinoma with EGFR Amplification Has Distinct Clinicopathologic and Molecular Features in Never-Smokers. Cancer Res.
69: 8341-8348
[Abstract][Full Text]
Nevo, J., Mattila, E., Pellinen, T., Yamamoto, D. L., Sara, H., Iljin, K., Kallioniemi, O., Bono, P., Heikkila, P., Joensuu, H., Warri, A., Ivaska, J.
(2009). Mammary-Derived Growth Inhibitor Alters Traffic of EGFR and Induces a Novel Form of Cetuximab Resistance. Clin. Cancer Res.
15: 6570-6581
[Abstract][Full Text]
Wang, W., Li, Q., Yamada, T., Matsumoto, K., Matsumoto, I., Oda, M., Watanabe, G., Kayano, Y., Nishioka, Y., Sone, S., Yano, S.
(2009). Crosstalk to Stromal Fibroblasts Induces Resistance of Lung Cancer to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. Clin. Cancer Res.
15: 6630-6638
[Abstract][Full Text]
Nishimura, M., Shin, M.-S., Singhirunnusorn, P., Suzuki, S., Kawanishi, M., Koizumi, K., Saiki, I., Sakurai, H.
(2009). TAK1-Mediated Serine/Threonine Phosphorylation of Epidermal Growth Factor Receptor via p38/Extracellular Signal-Regulated Kinase: NF-{kappa}B-Independent Survival Pathways in Tumor Necrosis Factor Alpha Signaling. Mol. Cell. Biol.
29: 5529-5539
[Abstract][Full Text]
Konstantinidou, G., Bey, E. A., Rabellino, A., Schuster, K., Maira, M. S., Gazdar, A. F., Amici, A., Boothman, D. A., Scaglioni, P. P.
(2009). Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Blockade Is an Effective Radiosensitizing Strategy for the Treatment of Non-Small Cell Lung Cancer Harboring K-RAS Mutations. Cancer Res.
69: 7644-7652
[Abstract][Full Text]
Zarrinkar, P. P., Gunawardane, R. N., Cramer, M. D., Gardner, M. F., Brigham, D., Belli, B., Karaman, M. W., Pratz, K. W., Pallares, G., Chao, Q., Sprankle, K. G., Patel, H. K., Levis, M., Armstrong, R. C., James, J., Bhagwat, S. S.
(2009). AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood
114: 2984-2992
[Abstract][Full Text]
Rudin, C. M., Avila-Tang, E., Harris, C. C., Herman, J. G., Hirsch, F. R., Pao, W., Schwartz, A. G., Vahakangas, K. H., Samet, J. M.
(2009). Lung Cancer in Never Smokers: Molecular Profiles and Therapeutic Implications. Clin. Cancer Res.
15: 5646-5661
[Abstract][Full Text]
Krishnaswamy, S., Kanteti, R., Duke-Cohan, J. S., Loganathan, S., Liu, W., Ma, P. C., Sattler, M., Singleton, P. A., Ramnath, N., Innocenti, F., Nicolae, D. L., Ouyang, Z., Liang, J., Minna, J., Kozloff, M. F., Ferguson, M. K., Natarajan, V., Wang, Y.-C., Garcia, J. G.N., Vokes, E. E., Salgia, R.
(2009). Ethnic Differences and Functional Analysis of MET Mutations in Lung Cancer. Clin. Cancer Res.
15: 5714-5723
[Abstract][Full Text]
Shaw, A. T., Yeap, B. Y., Mino-Kenudson, M., Digumarthy, S. R., Costa, D. B., Heist, R. S., Solomon, B., Stubbs, H., Admane, S., McDermott, U., Settleman, J., Kobayashi, S., Mark, E. J., Rodig, S. J., Chirieac, L. R., Kwak, E. L., Lynch, T. J., Iafrate, A. J.
(2009). Clinical Features and Outcome of Patients With Non-Small-Cell Lung Cancer Who Harbor EML4-ALK. JCO
27: 4247-4253
[Abstract][Full Text]
Horn, L., Pao, W.
(2009). EML4-ALK: Honing In on a New Target in Non-Small-Cell Lung Cancer. JCO
27: 4232-4235
[Full Text]
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., Nishiwaki, Y., Ohe, Y., Yang, J.-J., Chewaskulyong, B., Jiang, H., Duffield, E. L., Watkins, C. L., Armour, A. A., Fukuoka, M.
(2009). Gefitinib or Carboplatin-Paclitaxel in Pulmonary Adenocarcinoma. NEJM
361: 947-957
[Abstract][Full Text]
Rosell, R., Moran, T., Queralt, C., Porta, R., Cardenal, F., Camps, C., Majem, M., Lopez-Vivanco, G., Isla, D., Provencio, M., Insa, A., Massuti, B., Gonzalez-Larriba, J. L., Paz-Ares, L., Bover, I., Garcia-Campelo, R., Moreno, M. A., Catot, S., Rolfo, C., Reguart, N., Palmero, R., Sanchez, J. M., Bastus, R., Mayo, C., Bertran-Alamillo, J., Molina, M. A., Sanchez, J. J., Taron, M., the Spanish Lung Cancer Group,
(2009). Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer. NEJM
361: 958-967
[Abstract][Full Text]
Wozniak, A. J., Gadgeel, S. M.
(2009). Review: Adjuvant therapy for resected non-small cell lung cancer. Therapeutic Advances in Medical Oncology
1: 109-118
[Abstract]
Neyns, B., Sadones, J., Joosens, E., Bouttens, F., Verbeke, L., Baurain, J.-F., D'Hondt, L., Strauven, T., Chaskis, C., In't Veld, P., Michotte, A., De Greve, J.
(2009). Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol
20: 1596-1603
[Abstract][Full Text]
Ohashi, K., Takigawa, N., Osawa, M., Ichihara, E., Takeda, H., Kubo, T., Hirano, S., Yoshino, T., Takata, M., Tanimoto, M., Kiura, K.
(2009). Chemopreventive Effects of Gefitinib on Nonsmoking-Related Lung Tumorigenesis in Activating Epidermal Growth Factor Receptor Transgenic Mice. Cancer Res.
69: 7088-7095
[Abstract][Full Text]
Yoon, Y.-K., Kim, H.-P., Han, S.-W., Hur, H.-S., Oh, D. Y., Im, S.-A., Bang, Y.-J., Kim, T.-Y.
(2009). Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells. Molecular Cancer Therapeutics
8: 2526-2536
[Abstract][Full Text]
Pao, W., Kris, M. G., Iafrate, A. J., Ladanyi, M., Janne, P. A., Wistuba, I. I., Miake-Lye, R., Herbst, R. S., Carbone, D. P., Johnson, B. E., Lynch, T. J.
(2009). Integration of Molecular Profiling into the Lung Cancer Clinic. Clin. Cancer Res.
15: 5317-5322
[Abstract][Full Text]
Hama, T., Yuza, Y., Saito, Y., O-uchi, J., Kondo, S., Okabe, M., Yamada, H., Kato, T., Moriyama, H., Kurihara, S., Urashima, M.
(2009). Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma. The Oncologist
14: 900-908
[Abstract][Full Text]
Pallis, A. G., Gridelli, C., van Meerbeeck, J. P., Greillier, L., Wedding, U., Lacombe, D., Welch, J., Belani, C. P., Aapro, M.
(2009). EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts' opinion for the treatment of non-small-cell lung cancer in an elderly population. Ann Oncol
0: mdp360v1-mdp360
[Abstract][Full Text]
Finn, R. S., Press, M. F., Dering, J., Arbushites, M., Koehler, M., Oliva, C., Williams, L. S., Di Leo, A.
(2009). Estrogen Receptor, Progesterone Receptor, Human Epidermal Growth Factor Receptor 2 (HER2), and Epidermal Growth Factor Receptor Expression and Benefit From Lapatinib in a Randomized Trial of Paclitaxel With Lapatinib or Placebo As First-Line Treatment in HER2-Negative or Unknown Metastatic Breast Cancer. JCO
27: 3908-3915
[Abstract][Full Text]
Horn, L., Sandler, A.
(2009). Epidermal Growth Factor Receptor Inhibitors and Antiangiogenic Agents for the Treatment of Non-Small Cell Lung Cancer. Clin. Cancer Res.
15: 5040-5048
[Abstract][Full Text]
Rodig, S. J., Mino-Kenudson, M., Dacic, S., Yeap, B. Y., Shaw, A., Barletta, J. A., Stubbs, H., Law, K., Lindeman, N., Mark, E., Janne, P. A., Lynch, T., Johnson, B. E., Iafrate, A. J., Chirieac, L. R.
(2009). Unique Clinicopathologic Features Characterize ALK-Rearranged Lung Adenocarcinoma in the Western Population. Clin. Cancer Res.
15: 5216-5223
[Abstract][Full Text]
Jackman, D. M., Miller, V. A., Cioffredi, L.-A., Yeap, B. Y., Janne, P. A., Riely, G. J., Ruiz, M. G., Giaccone, G., Sequist, L. V., Johnson, B. E.
(2009). Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcomes in Previously Untreated Non-Small Cell Lung Cancer Patients: Results of an Online Tumor Registry of Clinical Trials. Clin. Cancer Res.
15: 5267-5273
[Abstract][Full Text]
Ocak, S., Sos, M. L., Thomas, R. K., Massion, P. P.
(2009). High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications. Eur Respir J
34: 489-506
[Abstract][Full Text]
Mishani, E., Hagooly, A.
(2009). Strategies for Molecular Imaging of Epidermal Growth Factor Receptor Tyrosine Kinase in Cancer. JNM
50: 1199-1202
[Abstract][Full Text]
Ko, J.-C., Ciou, S.-C., Jhan, J.-Y., Cheng, C.-M., Su, Y.-J., Chuang, S.-M., Lin, S.-T., Chang, C.-C., Lin, Y.-W.
(2009). Roles of MKK1/2-ERK1/2 and Phosphoinositide 3-Kinase-AKT Signaling Pathways in Erlotinib-Induced Rad51 Suppression and Cytotoxicity in Human Non-Small Cell Lung Cancer Cells. Mol Cancer Res
7: 1378-1389
[Abstract][Full Text]
Modrek, B., Ge, L., Pandita, A., Lin, E., Mohan, S., Yue, P., Guerrero, S., Lin, W. M., Pham, T., Modrusan, Z., Seshagiri, S., Stern, H. M., Waring, P., Garraway, L. A., Chant, J., Stokoe, D., Cavet, G.
(2009). Oncogenic Activating Mutations Are Associated with Local Copy Gain. Mol Cancer Res
7: 1244-1252
[Abstract][Full Text]
Pritchard, J. R., Cosgrove, B. D., Hemann, M. T., Griffith, L. G., Wands, J. R., Lauffenburger, D. A.
(2009). Three-kinase inhibitor combination recreates multipathway effects of a geldanamycin analogue on hepatocellular carcinoma cell death. Molecular Cancer Therapeutics
8: 2183-2192
[Abstract][Full Text]
Tam, I. Y.-S., Leung, E. L.-H., Tin, V. P.-C., Chua, D. T.-T., Sihoe, A. D.-L., Cheng, L.-C., Chung, L.-P., Wong, M. P.
(2009). Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared with common activating missense mutations. Molecular Cancer Therapeutics
8: 2142-2151
[Abstract][Full Text]
Seike, M., Goto, A., Okano, T., Bowman, E. D., Schetter, A. J., Horikawa, I., Mathe, E. A., Jen, J., Yang, P., Sugimura, H., Gemma, A., Kudoh, S., Croce, C. M., Harris, C. C.
(2009). MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc. Natl. Acad. Sci. USA
106: 12085-12090
[Abstract][Full Text]
Schmid, K., Oehl, N., Wrba, F., Pirker, R., Pirker, C., Filipits, M.
(2009). EGFR/KRAS/BRAF Mutations in Primary Lung Adenocarcinomas and Corresponding Locoregional Lymph Node Metastases. Clin. Cancer Res.
15: 4554-4560
[Abstract][Full Text]
Kawaguchi, K., Murakami, H., Taniguchi, T., Fujii, M., Kawata, S., Fukui, T., Kondo, Y., Osada, H., Usami, N., Yokoi, K., Ueda, Y., Yatabe, Y., Ito, M., Horio, Y., Hida, T., Sekido, Y.
(2009). Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells. Carcinogenesis
30: 1097-1105
[Abstract][Full Text]
Pantaleo, M. A, Nannini, M., Fanti, S., Boschi, S., Lollini, P.-L., Biasco, G.
(2009). Molecular Imaging of EGFR: It's Time to Go Beyond Receptor Expression. JNM
50: 1195-1196
[Full Text]
GARASSINO, M. C., BORGONOVO, K., ROSSI, A., MANCUSO, A., MARTELLI, O., TINAZZI, A., DI COSIMO, S., LA VERDE, N., SBURLATI, P., BIANCHI, C., FARINA, G., TORRI, V.
(2009). Biological and Clinical Features in Predicting Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Systematic Review and Meta-analysis. Anticancer Res
29: 2691-2701
[Abstract][Full Text]
SHUKUYA, T., TAKAHASHI, T., TAMIYA, A., ONO, A., IGAWA, S., NAKAMURA, Y., TSUYA, A., MURAKAMI, H., NAITO, T., KAIRA, K., ENDO, M., YAMAMOTO, N.
(2009). Gefitinib Plus Paclitaxel after Failure of Gefitinib in Non-small Cell Lung Cancer Initially Responding to Gefitinib. Anticancer Res
29: 2747-2751
[Abstract][Full Text]
PESEK, M., BENESOVA, L., BELSANOVA, B., MUKENSNABL, P., BRUHA, F., MINARIK, M.
(2009). Dominance of EGFR and Insignificant KRAS Mutations in Prediction of Tyrosine-kinase Therapy for NSCLC Patients Stratified by Tumor Subtype and Smoking Status. Anticancer Res
29: 2767-2773
[Abstract][Full Text]
Karpel-Massler, G., Schmidt, U., Unterberg, A., Halatsch, M.-E.
(2009). Therapeutic Inhibition of the Epidermal Growth Factor Receptor in High-Grade Gliomas: Where Do We Stand?. Mol Cancer Res
7: 1000-1012
[Abstract][Full Text]
Yang, L., Luo, H., Chen, J., Xing, Q., He, L.
(2009). SePreSA: a server for the prediction of populations susceptible to serious adverse drug reactions implementing the methodology of a chemical-protein interactome. Nucleic Acids Res
37: W406-W412
[Abstract][Full Text]
Versele, M., Talloen, W., Rockx, C., Geerts, T., Janssen, B., Lavrijssen, T., King, P., Gohlmann, H. W.H., Page, M., Perera, T.
(2009). Response prediction to a multitargeted kinase inhibitor in cancer cell lines and xenograft tumors using high-content tyrosine peptide arrays with a kinetic readout. Molecular Cancer Therapeutics
8: 1846-1855
[Abstract][Full Text]
Morita, S., Okamoto, I., Kobayashi, K., Yamazaki, K., Asahina, H., Inoue, A., Hagiwara, K., Sunaga, N., Yanagitani, N., Hida, T., Yoshida, K., Hirashima, T., Yasumoto, K., Sugio, K., Mitsudomi, T., Fukuoka, M., Nukiwa, T.
(2009). Combined Survival Analysis of Prospective Clinical Trials of Gefitinib for Non-Small Cell Lung Cancer with EGFR Mutations. Clin. Cancer Res.
15: 4493-4498
[Abstract][Full Text]
Choi, K., Ahn, Y.-H., Gibbons, D. L., Tran, H. T., Creighton, C. J., Girard, L., Minna, J. D., Qin, F. X.-F., Kurie, J. M.
(2009). Distinct Biological Roles for the Notch Ligands Jagged-1 and Jagged-2. J. Biol. Chem.
284: 17766-17774
[Abstract][Full Text]
Ichihara, E., Ohashi, K., Takigawa, N., Osawa, M., Ogino, A., Tanimoto, M., Kiura, K.
(2009). Effects of Vandetanib on Lung Adenocarcinoma Cells Harboring Epidermal Growth Factor Receptor T790M Mutation In vivo. Cancer Res.
69: 5091-5098
[Abstract][Full Text]
Brambilla, E., Gazdar, A.
(2009). Pathogenesis of lung cancer signalling pathways: roadmap for therapies. Eur Respir J
33: 1485-1497
[Abstract][Full Text]
Rossi, G., Pelosi, G., Graziano, P., Barbareschi, M., Papotti, M.
(2009). 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. INT J SURG PATHOL
17: 206-218
[Abstract]
Kotoula, V., Sozopoulos, E., Litsiou, H., Fanourakis, G., Koletsa, T., Voutsinas, G., Tseleni-Balafouta, S., Mitsiades, C. S, Wellmann, A., Mitsiades, N.
(2009). Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas. Endocr Relat Cancer
16: 565-572
[Abstract][Full Text]
Hogan, T., Jing Jie Yu, , Williams, H J., Altaha, R., Xiaobing Liang, , Qi He,
(2009). Oncocytic, focally anaplastic, thyroid cancer responding to erlotinib. J Oncol Pharm Pract
15: 111-117
[Abstract]
Bai, H., Mao, L., Wang, h. S., Zhao, J., Yang, L., An, t. T., Wang, X., Duan, c. J., Wu, n. M., Guo, z. Q., Liu, y. X., Liu, h. N., Wang, y. Y., Wang, J.
(2009). Epidermal Growth Factor Receptor Mutations in Plasma DNA Samples Predict Tumor Response in Chinese Patients With Stages IIIB to IV Non-Small-Cell Lung Cancer. JCO
27: 2653-2659
[Abstract][Full Text]
Sequist, L. V., Engelman, J. A., Lynch, T. J.
(2009). Toward Noninvasive Genomic Screening of Lung Cancer Patients. JCO
27: 2589-2591
[Full Text]
KUSUMOTO, S., SUGIYAMA, T., ANDO, K., HOSAKA, T., ISHIDA, H., SHIRAI, T., YAMAOKA, T., OKUDA, K., HIROSE, T., OHNISHI, T., INOUE, F., KANOME, T., KADOFUKU, T., SAIJO, N., ADACHII, M., OHMORI, T.
(2009). Combination Effect between Bortezomib and Tumor Necrosis Factor {alpha} on Gefitinib-resistant Non-small Cell Lung Cancer Cell Lines. Anticancer Res
29: 2315-2322
[Abstract][Full Text]
Leung, E. L.-H., Tam, I. Y.-S., Tin, V. P.-C., Chua, D. T.-T., Sihoe, A. D.-L., Cheng, L.-C., Ho, J. C.-M., Chung, L.-P., Wong, M. P.
(2009). Src Promotes Survival and Invasion of Lung Cancers with Epidermal Growth Factor Receptor Abnormalities and Is a Potential Candidate for Molecular-Targeted Therapy. Mol Cancer Res
7: 923-932
[Abstract][Full Text]
Freeman, D. J., Bush, T., Ogbagabriel, S., Belmontes, B., Juan, T., Plewa, C., Van, G., Johnson, C., Radinsky, R.
(2009). Activity of panitumumab alone or with chemotherapy in non-small cell lung carcinoma cell lines expressing mutant epidermal growth factor receptor. Molecular Cancer Therapeutics
8: 1536-1546
[Abstract][Full Text]
Herberger, B., Berger, W., Puhalla, H., Schmid, K., Novak, S., Brandstetter, A., Pirker, C., Gruenberger, T., Filipits, M.
(2009). Simultaneous blockade of the epidermal growth factor receptor/mammalian target of rapamycin pathway by epidermal growth factor receptor inhibitors and rapamycin results in reduced cell growth and survival in biliary tract cancer cells. Molecular Cancer Therapeutics
8: 1547-1556
[Abstract][Full Text]
Kaye, F. J.
(2009). Mutation-associated fusion cancer genes in solid tumors. Molecular Cancer Therapeutics
8: 1399-1408
[Abstract][Full Text]
Guillamo, J.-S., de Bouard, S., Valable, S., Marteau, L., Leuraud, P., Marie, Y., Poupon, M.-F., Parienti, J.-J., Raymond, E., Peschanski, M.
(2009). Molecular Mechanisms Underlying Effects of Epidermal Growth Factor Receptor Inhibition on Invasion, Proliferation, and Angiogenesis in Experimental Glioma. Clin. Cancer Res.
15: 3697-3704
[Abstract][Full Text]
Tyner, J. W., Deininger, M. W., Loriaux, M. M., Chang, B. H., Gotlib, J. R., Willis, S. G., Erickson, H., Kovacsovics, T., O'Hare, T., Heinrich, M. C., Druker, B. J.
(2009). RNAi screen for rapid therapeutic target identification in leukemia patients. Proc. Natl. Acad. Sci. USA
106: 8695-8700
[Abstract][Full Text]
Natale, R. B., Bodkin, D., Govindan, R., Sleckman, B. G., Rizvi, N. A., Capo, A., Germonpre, P., Eberhardt, W. E.E., Stockman, P. K., Kennedy, S. J., Ranson, M.
(2009). Vandetanib Versus Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: Results From a Two-Part, Double-Blind, Randomized Phase II Study. JCO
27: 2523-2529
[Abstract][Full Text]
Rickman, O. B., Vohra, P. K., Sanyal, B., Vrana, J. A., Aubry, M.-C., Wigle, D. A., Thomas, C. F. Jr.
(2009). Analysis of ErbB Receptors in Pulmonary Carcinoid Tumors. Clin. Cancer Res.
15: 3315-3324
[Abstract][Full Text]
Naumov, G. N., Nilsson, M. B., Cascone, T., Briggs, A., Straume, O., Akslen, L. A., Lifshits, E., Byers, L. A., Xu, L., Wu, H.-k., Janne, P., Kobayashi, S., Halmos, B., Tenen, D., Tang, X. M., Engelman, J., Yeap, B., Folkman, J., Johnson, B. E., Heymach, J. V.
(2009). 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.
15: 3484-3494
[Abstract][Full Text]
Borczuk, A. C.
(2009). Micropapillary Histology: A Frequent Morphology of Mutation-Associated Lung Adenocarcinoma?. Am J Clin Pathol
131: 615-617
[Full Text]
De Oliveira Duarte Achcar, R., Nikiforova, M. N., Yousem, S. A.
(2009). Micropapillary Lung Adenocarcinoma: EGFR, K-ras, and BRAF Mutational Profile. Am J Clin Pathol
131: 694-700
[Abstract][Full Text]
Sherman, S. I.
(2009). Advances in Chemotherapy of Differentiated Epithelial and Medullary Thyroid Cancers. J. Clin. Endocrinol. Metab.
94: 1493-1499
[Abstract][Full Text]
Yu, J., Kane, S., Wu, J., Benedettini, E., Li, D., Reeves, C., Innocenti, G., Wetzel, R., Crosby, K., Becker, A., Ferrante, M., Cheung, W. C., Hong, X., Chirieac, L. R., Sholl, L. M., Haack, H., Smith, B. L., Polakiewicz, R. D., Tan, Y., Gu, T.-L., Loda, M., Zhou, X., Comb, M. J.
(2009). Mutation-Specific Antibodies for the Detection of EGFR Mutations in Non-Small-Cell Lung Cancer. Clin. Cancer Res.
15: 3023-3028
[Abstract][Full Text]
Dy, G. K., Adjei, A. A.
(2009). Emerging Therapeutic Targets in Non-Small Cell Lung Cancer. Proc Am Thorac Soc
6: 218-223
[Abstract][Full Text]
Stinchcombe, T. E., Socinski, M. A.
(2009). Current Treatments for Advanced Stage Non-Small Cell Lung Cancer. Proc Am Thorac Soc
6: 233-241
[Abstract][Full Text]
Sartori, G., Cavazza, A., Sgambato, A., Marchioni, A., Barbieri, F., Longo, L., Bavieri, M., Murer, B., Meschiari, E., Tamberi, S., Cadioli, A., Luppi, F., Migaldi, M., Rossi, G.
(2009). EGFR and K-ras Mutations Along the Spectrum of Pulmonary Epithelial Tumors of the Lung and Elaboration of a Combined Clinicopathologic and Molecular Scoring System to Predict Clinical Responsiveness to EGFR Inhibitors. Am J Clin Pathol
131: 478-489
[Abstract][Full Text]
Ho, C. Y., MacRae, C. A.
(2009). Defining the Pathogenicity of DNA Sequence Variation. Circ Cardiovasc Genet
2: 95-97
[Full Text]
Chang, J. W., Asamura, H., Kawachi, R., Watanabe, S.-i.
(2009). Gender difference in survival of resected non-small cell lung cancer: Histology-related phenomenon?. J. Thorac. Cardiovasc. Surg.
137: 807-812
[Abstract][Full Text]
Medina, P. P., Castillo, S. D., Blanco, S., Sanz-Garcia, M., Largo, C., Alvarez, S., Yokota, J., Gonzalez-Neira, A., Benitez, J., Clevers, H. C., Cigudosa, J. C., Lazo, P. A., Sanchez-Cespedes, M.
(2009). The SRY-HMG box gene, SOX4, is a target of gene amplification at chromosome 6p in lung cancer. Hum Mol Genet
18: 1343-1352
[Abstract][Full Text]
Gow, C.-H., Chang, Y.-L., Hsu, Y.-C., Tsai, M.-F., Wu, C.-T., Yu, C.-J., Yang, C.-H., Lee, Y.-C., Yang, P.-C., Shih, J.-Y.
(2009). Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol
20: 696-702
[Abstract][Full Text]
KATAYAMA, K., SHIBATA, K., MITSUHASHI, J., NOGUCHI, K., SUGIMOTO, Y.
(2009). Pharmacological Interplay between Breast Cancer Resistance Protein and Gefitinib in Epidermal Growth Factor Receptor Signaling. Anticancer Res
29: 1059-1065
[Abstract][Full Text]
MAEGAWA, M., ARAO, T., YOKOTE, H., MATSUMOTO, K., KUDO, K., TANAKA, K., KANEDA, H., FUJITA, Y., ITO, F., NISHIO, K.
(2009). EGFR Mutation Up-regulates EGR1 Expression through the ERK Pathway. Anticancer Res
29: 1111-1117
[Abstract][Full Text]
YABUUCHI, S., KATAYOSE, Y., ODA, A., MIZUMA, M., SHIRASOU, S., SASAKI, T., YAMAMOTO, K., OIKAWA, M., RIKIYAMA, T., ONOGAWA, T., YOSHIDA, H., OHTUSKA, H., MOTOI, F., EGAWA, S., UNNO, M.
(2009). ZD1839 (IRESSA(R)) Stabilizes p27Kip1 and Enhances Radiosensitivity in Cholangiocarcinoma Cell Lines. Anticancer Res
29: 1169-1180
[Abstract][Full Text]
ROSSLER, J., ODENTHAL, E., GEOERGER, B., GERSTENMEYER, A., LAGODNY, J., NIEMEYER, C. M., VASSAL, G.
(2009). EGFR Inhibition Using Gefitinib Is Not Active in Neuroblastoma Cell Lines. Anticancer Res
29: 1327-1333
[Abstract][Full Text]
Kaulfuss, S., Burfeind, P., Gaedcke, J., Scharf, J.-G.
(2009). Dual silencing of insulin-like growth factor-I receptor and epidermal growth factor receptor in colorectal cancer cells is associated with decreased proliferation and enhanced apoptosis. Molecular Cancer Therapeutics
8: 821-833
[Abstract][Full Text]
Tan, D. S.P., Lambros, M. B.K., Rayter, S., Natrajan, R., Vatcheva, R., Gao, Q., Marchio, C., Geyer, F. C., Savage, K., Parry, S., Fenwick, K., Tamber, N., Mackay, A., Dexter, T., Jameson, C., McCluggage, W. G., Williams, A., Graham, A., Faratian, D., El-Bahrawy, M., Paige, A. J., Gabra, H., Gore, M. E., Zvelebil, M., Lord, C. J., Kaye, S. B., Ashworth, A., Reis-Filho, J. S.
(2009). PPM1D Is a Potential Therapeutic Target in Ovarian Clear Cell Carcinomas. Clin. Cancer Res.
15: 2269-2280
[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]
Yung, T. K.F., Chan, K.C. A., Mok, T. S.K., Tong, J., To, K.-F., Lo, Y.M. D.
(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]
van den Bent, M. J., Brandes, A. A., Rampling, R., Kouwenhoven, M. C.M., Kros, J. M., Carpentier, A. F., Clement, P. M., Frenay, M., Campone, M., Baurain, J.-F., Armand, J.-P., Taphoorn, M. J.B., Tosoni, A., Kletzl, H., Klughammer, B., Lacombe, D., Gorlia, T.
(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.
(2009). EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up. Eur Respir J
33: 436-440
[Abstract][Full Text]
Pantaleo, M. A., Nannini, M., Maleddu, A., Fanti, S., Nanni, C., Boschi, S., Lodi, F., Nicoletti, G., Landuzzi, L., Lollini, P. L., Biasco, G.
(2009). Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer. Ann Oncol
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]
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