© 2005 Oxford University Press
ARTICLE |
Epidermal Growth Factor Receptor Gene and Protein and Gefitinib Sensitivity in Non–Small-Cell Lung Cancer
Affiliations of authors: University of Colorado Health Sciences Center and University of Colorado Cancer Center, Aurora, CO (FC, FRH, LB, JH, SW, WAF, PAB, MVG); Bellaria Hospital, Bologna, Italy (FC, SB, EM, LC); CINECA Interuniversity Consortium, Bologna, Italy (ER, ID); Scientific Institute University Hospital San Raffaele, Milan, Italy (GLC, VG, CD); Response Genetic, Inc., Los Angeles, CA (KD); Policlinico Monteluce, Perugia, Italy (VL, AS, MT)
Correspondence to: Fred R. Hirsch, MD, PhD, University of Colorado Cancer Center, Department of Medicine and Pathology, 12801 E. 17th Ave., P.O. Box 6511, Mail Stop 8111, Aurora, CO 80010 (e-mail: fred.hirsch{at}uchsc.edu).
Background: Gefitinib is a selective inhibitor of the epidermal growth factor (EGFR) tyrosine kinase, which is overexpressed in many cancers, including non–small-cell lung cancer (NSCLC). We carried out a clinical study to compare the relationship between EGFR gene copy number, EGFR protein expression, EGFR mutations, and Akt activation status as predictive markers for gefitinib therapy in advanced NSCLC. Methods: Tumors from 102 NSCLC patients treated daily with 250 mg of gefitinib were evaluated for EGFR status by fluorescence in situ hybridization (FISH), DNA sequencing, and immunohistochemistry and for Akt activation status (phospho-Akt [P-Akt]) by immunohistochemistry. Time to progression, overall survival, and 95% confidence intervals (CIs) were calculated and evaluated by the Kaplan–Meier method; groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. All statistical tests were two-sided. Results: Amplification or high polysomy of the EGFR gene (seen in 33 of 102 patients) and high protein expression (seen in 58 of 98 patients) were statistically significantly associated with better response (36% versus 3%, mean difference = 34%, 95% CI = 16.6 to 50.3; P<.001), disease control rate (67% versus 26%, mean difference = 40.6%, 95% CI = 21.5 to 59.7; P<.001), time to progression (9.0 versus 2.5 months, mean difference = 6.5 months, 95% CI = 2.8 to 10.3; P<.001), and survival (18.7 versus 7.0 months, mean difference = 11.7 months, 95% CI = 2.1 to 21.4; P = .03). EGFR mutations (seen in 15 of 89 patients) were also statistically significantly related to response and time to progression, but the association with survival was not statistically significant, and 40% of the patients with mutation had progressive disease. In multivariable analysis, only high EGFR gene copy number remained statistically significantly associated with better survival (hazard ratio = 0.44, 95% CI = 0.23 to 0.82). Independent of EGFR assessment method, EGFR+/P-Akt+ patients had a statistically significantly better outcome than EGFR–, P-Akt–, or EGFR+/P-Akt– patients. Conclusions: High EGFR gene copy number identified by FISH may be an effective molecular predictor for gefitinib efficacy in advanced NSCLC.
CiteULike 
Connotea 
Del.icio.us What's this?
Editorial about this Article
- A Curious Link Between Epidermal Growth Factor Receptor Amplification and Survival: Effect of "Allele Dilution" on Gefitinib Sensitivity?
- Frederic J. Kaye
J Natl Cancer Inst 2005 97: 621-623.[Extract] [Full Text] [PDF]
Related Memo to the Media
- Press Release: Study Identifies Possible Marker for Efficacy of Gefitinib in Lung Cancer Patients
- Sarah L. Zielinski
J Natl Cancer Inst 2005 97: 617.[Extract] [Full Text]
This article has been cited by other articles:
|
|
 |
|
  M. S. Gordon, M. Hussey, R. B. Nagle, P. N. Lara Jr, P. C. Mack, J. Dutcher, W. Samlowski, J. I. Clark, D. I. Quinn, C.-X. Pan, et al. Phase II Study of Erlotinib in Patients With Locally Advanced or Metastatic Papillary Histology Renal Cell Cancer: SWOG S0317 J. Clin. Oncol., December 1, 2009; 27(34): 5788 - 5793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Leidner, P. Fu, B. Clifford, A. Hamdan, C. Jin, R. Eisenberg, T. J. Boggon, M. Skokan, W. A. Franklin, F. Cappuzzo, et al. Genetic Abnormalities of the EGFR Pathway in African American Patients With Non-Small-Cell Lung Cancer J. Clin. Oncol., November 20, 2009; 27(33): 5620 - 5626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Peled, K. Yoshida, M. W. Wynes, and F. R. Hirsch Review: Predictive and prognostic markers for epidermal growth factor receptor inhibitor therapy in non-small cell lung cancer Therapeutic Advances in Medical Oncology, November 1, 2009; 1(3): 137 - 144. [Abstract] [PDF]
|
|
|
|
 |
|
 M Varella-Garcia, J Diebold, D A Eberhard, K Geenen, A Hirschmann, M Kockx, I Nagelmeier, J Ruschoff, M Schmitt, S Arbogast, et al. EGFR fluorescence in situ hybridisation assay: guidelines for application to non-small-cell lung cancer J. Clin. Pathol., November 1, 2009; 62(11): 970 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Sholl, B. Y. Yeap, A. J. Iafrate, A. J. Holmes-Tisch, Y.-P. Chou, M.-T. Wu, Y.-G. Goan, L. Su, E. Benedettini, J. Yu, et al. Lung Adenocarcinoma with EGFR Amplification Has Distinct Clinicopathologic and Molecular Features in Never-Smokers Cancer Res., November 1, 2009; 69(21): 8341 - 8348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S.K. Mok, Y.-L. Wu, C.-J. Yu, C. Zhou, Y.-M. Chen, L. Zhang, J. Ignacio, M. Liao, V. Srimuninnimit, M. J. Boyer, et al. Randomized, Placebo-Controlled, Phase II Study of Sequential Erlotinib and Chemotherapy As First-Line Treatment for Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., October 20, 2009; 27(30): 5080 - 5087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Wagner, S. Perner, D. S. Rickman, C. J. LaFargue, N. Kitabayashi, S. F. Johnstone, B. A. Weir, M. Meyerson, N. K. Altorki, and M. A. Rubin In Situ Evidence of KRAS Amplification and Association With Increased p21 Levels in Non-Small Cell Lung Carcinoma Am J Clin Pathol, October 1, 2009; 132(4): 500 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cappuzzo, G. Tallini, G. Finocchiaro, R. S. Wilson, C. Ligorio, L. Giordano, L. Toschi, M. Incarbone, R. Cavina, L. Terracciano, et al. Insulin-like growth factor receptor 1 (IGF1R) expression and survival in surgically resected non-small-cell lung cancer (NSCLC) patients Ann. Onc., September 18, 2009; (2009) mdp357v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Wozniak and S. M. Gadgeel Review: Adjuvant therapy for resected non-small cell lung cancer Therapeutic Advances in Medical Oncology, September 1, 2009; 1(2): 109 - 118. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Horn and A. Sandler Epidermal Growth Factor Receptor Inhibitors and Antiangiogenic Agents for the Treatment of Non-Small Cell Lung Cancer Clin. Cancer Res., August 15, 2009; 15(16): 5040 - 5048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Jackman, V. A. Miller, L.-A. Cioffredi, B. Y. Yeap, P. A. Janne, G. J. Riely, M. G. Ruiz, G. Giaccone, L. V. Sequist, and B. E. Johnson 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., August 15, 2009; 15(16): 5267 - 5273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Modrek, L. Ge, A. Pandita, E. Lin, S. Mohan, P. Yue, S. Guerrero, W. M. Lin, T. Pham, Z. Modrusan, et al. Oncogenic Activating Mutations Are Associated with Local Copy Gain Mol. Cancer Res., August 1, 2009; 7(8): 1244 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Kim, S.-Y. Park, and H. Pyo Cyclooxygenase-2 (COX-2) Negatively Regulates Expression of Epidermal Growth Factor Receptor and Causes Resistance to Gefitinib in COX-2-Overexpressing Cancer Cells Mol. Cancer Res., August 1, 2009; 7(8): 1367 - 1377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sun, C. Behrens, L. Feng, N. Ozburn, X. Tang, G. Yin, R. Komaki, M. Varella-Garcia, W. K. Hong, K. D. Aldape, et al. HER Family Receptor Abnormalities in Lung Cancer Brain Metastases and Corresponding Primary Tumors Clin. Cancer Res., August 1, 2009; 15(15): 4829 - 4837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. GARASSINO, K. BORGONOVO, A. ROSSI, A. MANCUSO, O. MARTELLI, A. TINAZZI, S. DI COSIMO, N. LA VERDE, P. SBURLATI, C. BIANCHI, et al. Biological and Clinical Features in Predicting Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Systematic Review and Meta-analysis Anticancer Res, July 1, 2009; 29(7): 2691 - 2701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rossi, G. Pelosi, P. Graziano, M. Barbareschi, and M. Papotti 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 International Journal of Surgical Pathology, June 1, 2009; 17(3): 206 - 218. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Tassinari, E. Scarpi, S. Sartori, E. Tamburini, C. Santelmo, P. Tombesi, and L. Lazzari-Agli Second-Line Treatments in Non-small Cell Lung Cancer: A Systematic Review of Literature and Metaanalysis of Randomized Clinical Trials Chest, June 1, 2009; 135(6): 1596 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. De Oliveira Duarte Achcar, M. N. Nikiforova, and S. A. Yousem Micropapillary Lung Adenocarcinoma: EGFR, K-ras, and BRAF Mutational Profile Am J Clin Pathol, May 1, 2009; 131(5): 694 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Goss, D. Ferry, R. Wierzbicki, S. A. Laurie, J. Thompson, B. Biesma, F. R. Hirsch, M. Varella-Garcia, E. Duffield, O. U. Ataman, et al. Randomized Phase II Study of Gefitinib Compared With Placebo in Chemotherapy-Naive Patients With Advanced Non-Small-Cell Lung Cancer and Poor Performance Status J. Clin. Oncol., May 1, 2009; 27(13): 2253 - 2260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ludovini, G. Bellezza, L. Pistola, F. Bianconi, L. Di Carlo, A. Sidoni, A. Semeraro, R. Del Sordo, F. R. Tofanetti, M. G. Mameli, et al. High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients Ann. Onc., May 1, 2009; 20(5): 842 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. W. Stewart, E. E.W. Cohen, L. Licitra, C. M.L. Van Herpen, C. Khorprasert, D. Soulieres, P. Vodvarka, D. Rischin, A. M. Garin, F. R. Hirsch, et al. Phase III Study of Gefitinib Compared With Intravenous Methotrexate for Recurrent Squamous Cell Carcinoma of the Head and Neck J. Clin. Oncol., April 10, 2009; 27(11): 1864 - 1871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cappuzzo, A. Marchetti, M. Skokan, E. Rossi, S. Gajapathy, L. Felicioni, M. del Grammastro, M. G. Sciarrotta, F. Buttitta, M. Incarbone, et al. Increased MET Gene Copy Number Negatively Affects Survival of Surgically Resected Non-Small-Cell Lung Cancer Patients J. Clin. Oncol., April 1, 2009; 27(10): 1667 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Martin, L Mazzucchelli, and M Frattini An overview of the epidermal growth factor receptor fluorescence in situ hybridisation challenge in tumour pathology J. Clin. Pathol., April 1, 2009; 62(4): 314 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cappuzzo, P. A. Janne, M. Skokan, G. Finocchiaro, E. Rossi, C. Ligorio, P. A. Zucali, L. Terracciano, L. Toschi, M. Roncalli, et al. MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients Ann. Onc., February 1, 2009; 20(2): 298 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Pantaleo, M. Nannini, A. Maleddu, S. Fanti, C. Nanni, S. Boschi, F. Lodi, G. Nicoletti, L. Landuzzi, P. L. Lollini, et al. Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer Ann. Onc., February 1, 2009; 20(2): 213 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takano, S. Ota, A. Hori, N. Seki, and K. Eguchi Can Epidermal Growth Factor Receptor-Fluorescent in Situ Hybridization Predict Clinical Benefit From Cetuximab Treatment in Patients With Non-Small-Cell Lung Cancer? J. Clin. Oncol., January 20, 2009; 27(3): 464 - 465. [Full Text] [PDF]
|
|
|
|
|
|
F. R. Hirsch, R. S. Herbst, C. Olsen, K. Chansky, J. Crowley, K. Kelly, W. A. Franklin, P. A. Bunn Jr, M. Varella-Garcia, and D. R. Gandara In Reply J. Clin. Oncol., January 20, 2009; 27(3): 465 - 467. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 M. A. Socinski 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? ASCO Educational Book, January 1, 2009; 2009(1): 436 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Sohn, Y.-J. Yang, J.-S. Ryu, S. J. Oh, K. C. Im, D. H. Moon, D. H. Lee, C. Suh, J.-S. Lee, and S.-W. Kim [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., November 15, 2008; 14(22): 7423 - 7429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yonesaka, K. Zejnullahu, N. Lindeman, A. J. Homes, D. M. Jackman, F. Zhao, A. M. Rogers, B. E. Johnson, and P. A. Janne Autocrine Production of Amphiregulin Predicts Sensitivity to Both Gefitinib and Cetuximab in EGFR Wild-type Cancers Clin. Cancer Res., November 1, 2008; 14(21): 6963 - 6973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Fichtner, J. Rolff, R. Soong, J. Hoffmann, S. Hammer, A. Sommer, M. Becker, and J. Merk Establishment of Patient-Derived Non-Small Cell Lung Cancer Xenografts as Models for the Identification of Predictive Biomarkers Clin. Cancer Res., October 15, 2008; 14(20): 6456 - 6468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Mack, M. W. Redman, K. Chansky, S. K. Williamson, N. C. Farneth, P. N. Lara Jr, W. A. Franklin, Q.-T. Le, J. J. Crowley, and D. R. Gandara Lower Osteopontin Plasma Levels Are Associated With Superior Outcomes in Advanced Non-Small-Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy: SWOG Study S0003 J. Clin. Oncol., October 10, 2008; 26(29): 4771 - 4776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Tedford, F. M. White, and J. A. Radding Illuminating signaling network functional biology through quantitative phosphoproteomic mass spectrometry Brief Funct Genomic Proteomic, October 4, 2008; (2008) eln037v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S-G. Wu, C-H. Gow, C-J. Yu, Y-L. Chang, C-H. Yang, Y-C. Hsu, J-Y. Shih, Y-C. Lee, and P-C. Yang Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma Eur. Respir. J., October 1, 2008; 32(4): 924 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Hirsch, M. Varella-Garcia, R. Dziadziuszko, Y. Xiao, S. Gajapathy, M. Skokan, M. Lin, V. O'Neill, and P. A. Bunn Jr. Fluorescence In situ Hybridization Subgroup Analysis of TRIBUTE, a Phase III Trial of Erlotinib Plus Carboplatin and Paclitaxel in Non-Small Cell Lung Cancer Clin. Cancer Res., October 1, 2008; 14(19): 6317 - 6323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C M West, L Joseph, and S Bhana Epidermal growth factor receptor-targeted therapy Br. J. Radiol., October 1, 2008; 81(Special_Issue_1): S36 - S44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Personeni, S. Fieuws, H. Piessevaux, G. De Hertogh, J. De Schutter, B. Biesmans, W. De Roock, A. Capoen, M. Debiec-Rychter, J.-L. Van Laethem, et al. Clinical Usefulness of EGFR Gene Copy Number as a Predictive Marker in Colorectal Cancer Patients Treated with Cetuximab: A Fluorescent In situ Hybridization Study Clin. Cancer Res., September 15, 2008; 14(18): 5869 - 5876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maruyama, Y. Nishiwaki, T. Tamura, N. Yamamoto, M. Tsuboi, K. Nakagawa, T. Shinkai, S. Negoro, F. Imamura, K. Eguchi, et al. Phase III Study, V-15-32, of Gefitinib Versus Docetaxel in Previously Treated Japanese Patients With Non-Small-Cell Lung Cancer J. Clin. Oncol., September 10, 2008; 26(26): 4244 - 4252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Crino, F. Cappuzzo, P. Zatloukal, M. Reck, M. Pesek, J. C. Thompson, H. E.R. Ford, F. R. Hirsch, M. Varella-Garcia, S. Ghiorghiu, et al. Gefitinib Versus Vinorelbine in Chemotherapy-Naive Elderly Patients With Advanced Non-Small-Cell Lung Cancer (INVITE): A Randomized, Phase II Study J. Clin. Oncol., September 10, 2008; 26(26): 4253 - 4260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Q. Zhu, G. da Cunha Santos, K. Ding, A. Sakurada, J.-C. Cutz, N. Liu, T. Zhang, P. Marrano, M. Whitehead, J. A. Squire, et al. Role of KRAS and EGFR As Biomarkers of Response to Erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21 J. Clin. Oncol., September 10, 2008; 26(26): 4268 - 4275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Van Dyke, M. L. Cote, G. M. Prysak, G. B. Claeys, A. S. Wenzlaff, V. C. Murphy, F. Lonardo, and A. G. Schwartz COX-2/EGFR expression and survival among women with adenocarcinoma of the lung Carcinogenesis, September 1, 2008; 29(9): 1781 - 1787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Stinchcombe and M. A. Socinski Gefitinib in Advanced Non-Small Cell Lung Cancer: Does It Deserve a Second Chance? Oncologist, September 1, 2008; 13(9): 933 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Liu, P. Hou, M. Ji, H. Guan, K. Studeman, K. Jensen, V. Vasko, A. K. El-Naggar, and M. Xing Highly Prevalent Genetic Alterations in Receptor Tyrosine Kinases and Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase Pathways in Anaplastic and Follicular Thyroid Cancers J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3106 - 3116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Tang, M. Varella-Garcia, A. C. Xavier, E. Massarelli, N. Ozburn, C. Moran, and I. I. Wistuba Epidermal Growth Factor Receptor Abnormalities in the Pathogenesis and Progression of Lung Adenocarcinomas Cancer Prevention Research, August 1, 2008; 1(3): 192 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Hirsch, R. S. Herbst, C. Olsen, K. Chansky, J. Crowley, K. Kelly, W. A. Franklin, P. A. Bunn Jr, M. Varella-Garcia, and D. R. Gandara Increased EGFR Gene Copy Number Detected by Fluorescent In Situ Hybridization Predicts Outcome in Non-Small-Cell Lung Cancer Patients Treated With Cetuximab and Chemotherapy J. Clin. Oncol., July 10, 2008; 26(20): 3351 - 3357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-J. Ahn, B.-B. Park, J. S. Ahn, S. W. Kim, H.-T. Kim, J. S. Lee, J. H. Kang, J. Y. Cho, H. S. Song, S. H. Park, et al. Are There Any Ethnic Differences in Molecular Predictors of Erlotinib Efficacy in Advanced Non-Small Cell Lung Cancer? Clin. Cancer Res., June 15, 2008; 14(12): 3860 - 3866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Felip, F. Rojo, M. Reck, A. Heller, B. Klughammer, G. Sala, S. Cedres, S. Peralta, H. Maacke, D. Foernzler, et al. A Phase II Pharmacodynamic Study of Erlotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy Clin. Cancer Res., June 15, 2008; 14(12): 3867 - 3874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Yang, C.-J. Yu, J.-Y. Shih, Y.-C. Chang, F.-C. Hu, M.-C. Tsai, K.-Y. Chen, Z.-Z. Lin, C.-J. Huang, C.-T. Shun, et al. Specific EGFR Mutations Predict Treatment Outcome of Stage IIIB/IV Patients With Chemotherapy-Naive Non-Small-Cell Lung Cancer Receiving First-Line Gefitinib Monotherapy J. Clin. Oncol., June 1, 2008; 26(16): 2745 - 2753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Sequist, R. G. Martins, D. Spigel, S. M. Grunberg, A. Spira, P. A. Janne, V. A. Joshi, D. McCollum, T. L. Evans, A. Muzikansky, et al. First-Line Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer Harboring Somatic EGFR Mutations J. Clin. Oncol., May 20, 2008; 26(15): 2442 - 2449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Engelman and P. A. Janne Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer Clin. Cancer Res., May 15, 2008; 14(10): 2895 - 2899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Mueller, L. A. Hunter, S. P. Ethier, and J. L. Boerner Met and c-Src Cooperate to Compensate for Loss of Epidermal Growth Factor Receptor Kinase Activity in Breast Cancer Cells Cancer Res., May 1, 2008; 68(9): 3314 - 3322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. Labianca, M. Garassino, and V. Torri Predicting response of molecular targeted therapies: a still possible challenge? Ann. Onc., May 1, 2008; 19(5): 829 - 830. [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Li, D. Chitale, G. J. Riely, W. Pao, V. A. Miller, M. F. Zakowski, V. Rusch, M. G. Kris, and M. Ladanyi EGFR Mutations in Lung Adenocarcinomas: Clinical Testing Experience and Relationship to EGFR Gene Copy Number and Immunohistochemical Expression J. Mol. Diagn., May 1, 2008; 10(3): 242 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jimeno, A. C. Tan, J. Coffa, N.V. Rajeshkumar, P. Kulesza, B. Rubio-Viqueira, J. Wheelhouse, B. Diosdado, W. A. Messersmith, C. Iacobuzio-Donahue, et al. Coordinated Epidermal Growth Factor Receptor Pathway Gene Overexpression Predicts Epidermal Growth Factor Receptor Inhibitor Sensitivity in Pancreatic Cancer Cancer Res., April 15, 2008; 68(8): 2841 - 2849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
Y. Yatabe, T. Takahashi, and T. Mitsudomi Epidermal Growth Factor Receptor Gene Amplification Is Acquired in Association with Tumor Progression of EGFR-Mutated Lung Cancer Cancer Res., April 1, 2008; 68(7): 2106 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Fuchs, T. Fujii, J. D. Dorfman, J. M. Goodwin, A. X. Zhu, M. Lanuti, and K. K. Tanabe Epithelial-to-Mesenchymal Transition and Integrin-Linked Kinase Mediate Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Hepatoma Cells Cancer Res., April 1, 2008; 68(7): 2391 - 2399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Gilbert, M. P. Goetz, C. A. Reynolds, J. N. Ingle, K. F. Giordano, V. J. Suman, H. E. Blair, R. B. Jenkins, W. L. Lingle, M. M. Reinholz, et al. Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy Mol. Cancer Ther., April 1, 2008; 7(4): 944 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cappuzzo, G. Finocchiaro, E. Rossi, P.A. Janne, C. Carnaghi, C. Calandri, K. Bencardino, C. Ligorio, F. Ciardiello, T. Pressiani, et al. EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients Ann. Onc., April 1, 2008; 19(4): 717 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D'Addario, D. Rauch, R. Stupp, M. Pless, R. Stahel, N. Mach, L. Jost, L. Widmer, C. Tapia, M. Bihl, et al. Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03 Ann. Onc., April 1, 2008; 19(4): 739 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. I. Na, B. H. Byun, H. J. Kang, G. J. Cheon, J. S. Koh, C. H. Kim, D. H. Choe, B.-Y. Ryoo, J. C. Lee, S. M. Lim, et al. 18F-Fluoro-2-Deoxy-Glucose Uptake Predicts Clinical Outcome in Patients with Gefitinib-Treated Non-Small Cell Lung Cancer Clin. Cancer Res., April 1, 2008; 14(7): 2036 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Fidler, A. Argiris, J. D. Patel, D. H. Johnson, A. Sandler, V. M. Villaflor, J. Coon IV, L. Buckingham, K. Kaiser, S. Basu, et al. The Potential Predictive Value of Cyclooxygenase-2 Expression and Increased Risk of Gastrointestinal Hemorrhage in Advanced Non-Small Cell Lung Cancer Patients Treated with Erlotinib and Celecoxib Clin. Cancer Res., April 1, 2008; 14(7): 2088 - 2094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ciardiello and G. Tortora EGFR Antagonists in Cancer Treatment N. Engl. J. Med., March 13, 2008; 358(11): 1160 - 1174. [Full Text] [PDF]
|
|
|
|
|
|
F. Pinter, J. Papay, A. Almasi, Z. Sapi, E. Szabo, M. Kanya, A. Tamasi, B. Jori, E. Varkondi, J. Moldvay, et al. Epidermal Growth Factor Receptor (EGFR) High Gene Copy Number and Activating Mutations in Lung Adenocarcinomas Are Not Consistently Accompanied by Positivity for EGFR Protein by Standard Immunohistochemistry J. Mol. Diagn., March 1, 2008; 10(2): 160 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Black, G. A. Brown, T. Inamoto, M. Shrader, A. Arora, A. O. Siefker-Radtke, L. Adam, D. Theodorescu, X. Wu, M. F. Munsell, et al. Sensitivity to Epidermal Growth Factor Receptor Inhibitor Requires E-Cadherin Expression in Urothelial Carcinoma Cells Clin. Cancer Res., March 1, 2008; 14(5): 1478 - 1486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Eberhard, G. Giaccone, and B. E. Johnson Biomarkers of Response to Epidermal Growth Factor Receptor Inhibitors in Non-Small-Cell Lung Cancer Working Group: Standardization for Use in the Clinical Trial Setting J. Clin. Oncol., February 20, 2008; 26(6): 983 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Brandes, E. Franceschi, A. Tosoni, M. E. Hegi, and R. Stupp Epidermal Growth Factor Receptor Inhibitors in Neuro-oncology: Hopes and Disappointments Clin. Cancer Res., February 15, 2008; 14(4): 957 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. Merchant, I. Voskresensky, C. M. Rogers, B. LaFleur, P. J. Dempsey, R. Graves-Deal, F. Revetta, A. C. Foutch, M. L. Rothenberg, M. K. Washington, et al. TACE/ADAM-17: A Component of the Epidermal Growth Factor Receptor Axis and a Promising Therapeutic Target in Colorectal Cancer Clin. Cancer Res., February 15, 2008; 14(4): 1182 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cavazzoni, R. R. Alfieri, C. Carmi, V. Zuliani, M. Galetti, C. Fumarola, R. Frazzi, M. Bonelli, F. Bordi, A. Lodola, et al. Dual mechanisms of action of the 5-benzylidene-hydantoin UPR1024 on lung cancer cell lines Mol. Cancer Ther., February 1, 2008; 7(2): 361 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Bunn Jr. and N. Thatcher Introduction Oncologist, January 1, 2008; 13(suppl_1): 1 - 4. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. de Marinis and F. Grossi Clinical Evidence for Second- and Third-Line Treatment Options in Advanced Non-Small Cell Lung Cancer Oncologist, January 1, 2008; 13(suppl_1): 14 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Bunn Jr. and N. Thatcher Conclusion Oncologist, January 1, 2008; 13(suppl_1): 37 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Engelman, K. Zejnullahu, C.-M. Gale, E. Lifshits, A. J. Gonzales, T. Shimamura, F. Zhao, P. W. Vincent, G. N. Naumov, J. E. Bradner, et al. PF00299804, an Irreversible Pan-ERBB Inhibitor, Is Effective in Lung Cancer Models with EGFR and ERBB2 Mutations that Are Resistant to Gefitinib Cancer Res., December 15, 2007; 67(24): 11924 - 11932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Thomas, P. Rochaix, A. Benlyazid, J. Sarini, M. Rives, J. L. Lefebvre, B. C. Allal, F. Courbon, E. Chatelut, and J.-P. Delord Pilot Study of Neoadjuvant Treatment with Erlotinib in Nonmetastatic Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., December 1, 2007; 13(23): 7086 - 7092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Schlomm, P. Kirstein, L. Iwers, B. Daniel, T. Steuber, J. Walz, F. H.K. Chun, A. Haese, J. Kollermann, M. Graefen, et al. Clinical Significance of Epidermal Growth Factor Receptor Protein Overexpression and Gene Copy Number Gains in Prostate Cancer Clin. Cancer Res., November 15, 2007; 13(22): 6579 - 6584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Liu, X. Wu, W. Zhang, R. C. Montenegro, D. L. Fackenthal, J. A. Spitz, L. M. Huff, F. Innocenti, S. Das, E. H. Cook, Jr., et al. Relationship of EGFR Mutations, Expression, Amplification, and Polymorphisms to Epidermal Growth Factor Receptor Inhibitors in the NCI60 Cell Lines Clin. Cancer Res., November 15, 2007; 13(22): 6788 - 6795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Loprevite, M. Tiseo, M. Chiaramondia, M. Capelletti, C. Bozzetti, B. Bortesi, N. Naldi, R. Nizzoli, P. Dadati, A. Kunkl, et al. Buccal Mucosa Cells as In vivo Model to Evaluate Gefitinib Activity in Patients with Advanced Non Small Cell Lung Cancer Clin. Cancer Res., November 1, 2007; 13(21): 6518 - 6526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Suzuki, H. Shigematsu, T. Nakajima, R. Kubo, S. Motohashi, Y. Sekine, K. Shibuya, T. Iizasa, K. Hiroshima, Y. Nakatani, et al. Synchronous Alterations of Wnt and Epidermal Growth Factor Receptor Signaling Pathways through Aberrant Methylation and Mutation in Non Small Cell Lung Cancer Clin. Cancer Res., October 15, 2007; 13(20): 6087 - 6092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Herbst, A. M. Davies, R. B. Natale, T. P. Dang, J. H. Schiller, L. L. Garland, V. A. Miller, D. Mendelson, A. D. Van den Abbeele, Y. Melenevsky, et al. Efficacy and Safety of Single-Agent Pertuzumab, a Human Epidermal Receptor Dimerization Inhibitor, in Patients with Non Small Cell Lung Cancer Clin. Cancer Res., October 15, 2007; 13(20): 6175 - 6181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takano, Y. Ohe, K. Tsuta, T. Fukui, H. Sakamoto, T. Yoshida, U. Tateishi, H. Nokihara, N. Yamamoto, I. Sekine, et al. Epidermal Growth Factor Receptor Mutation Detection Using High-Resolution Melting Analysis Predicts Outcomes in Patients with Advanced Non Small Cell Lung Cancer Treated with Gefitinib Clin. Cancer Res., September 15, 2007; 13(18): 5385 - 5390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Janne, J. von Pawel, R. B. Cohen, L. Crino, C. A. Butts, S. S. Olson, I. A. Eiseman, A. A. Chiappori, B. Y. Yeap, P. F. Lenehan, et al. Multicenter, Randomized, Phase II Trial of CI-1033, an Irreversible Pan-ERBB Inhibitor, for Previously Treated Advanced Non Small-Cell Lung Cancer J. Clin. Oncol., September 1, 2007; 25(25): 3936 - 3944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Khambata-Ford, C. R. Garrett, N. J. Meropol, M. Basik, C. T. Harbison, S. Wu, T. W. Wong, X. Huang, C. H. Takimoto, A. K. Godwin, et al. Expression of Epiregulin and Amphiregulin and K-ras Mutation Status Predict Disease Control in Metastatic Colorectal Cancer Patients Treated With Cetuximab J. Clin. Oncol., August 1, 2007; 25(22): 3230 - 3237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Lee, G. K. Lee, S.-y. Kong, M. C. Kook, S. K. Yang, S. Y. Park, S. H. Park, B. Keam, D. J. Park, B. Y. Cho, et al. Epidermal growth factor receptor status in anaplastic thyroid carcinoma J. Clin. Pathol., August 1, 2007; 60(8): 881 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Bonomi, L. Buckingham, and J. Coon Selecting Patients for Treatment with Epidermal Growth Factor Tyrosine Kinase Inhibitors Clin. Cancer Res., August 1, 2007; 13(15): 4606s - 4612s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Johnson, D. Jackman, and P. A. Janne Rationale for a Phase I Trial of Erlotinib and the Mammalian Target of Rapamycin Inhibitor Everolimus (RAD001) for Patients with Relapsed Non Small Cell Lung Cancer Clin. Cancer Res., August 1, 2007; 13(15): 4628s - 4631s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Karamouzis, J. R. Grandis, and A. Argiris Therapies Directed Against Epidermal Growth Factor Receptor in Aerodigestive Carcinomas JAMA, July 4, 2007; 298(1): 70 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Wiencke, S. Zheng, N. Jelluma, T. Tihan, S. Vandenberg, T. Tamguney, R. Baumber, R. Parsons, K. R. Lamborn, M. S. Berger, et al. Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma Neuro-oncol, July 1, 2007; 9(3): 271 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Torigian, S. S. Huang, M. Houseni, and A. Alavi Functional Imaging of Cancer with Emphasis on Molecular Techniques CA Cancer J Clin, July 1, 2007; 57(4): 206 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Finberg, L. V. Sequist, V. A. Joshi, A. Muzikansky, J. M. Miller, M. Han, J. Beheshti, L. R. Chirieac, E. J. Mark, and A. J. Iafrate Mucinous Differentiation Correlates with Absence of EGFR Mutation and Presence of KRAS Mutation in Lung Adenocarcinomas with Bronchioloalveolar Features J. Mol. Diagn., July 1, 2007; 9(3): 320 - 326. [Abstract] [Full Text] [PDF]
|
|