Originally published as JCO Early Release 10.1200/JCO.2005.11.890 on March 7 2005

This Article Full Text Full Text (PDF) Erratum (v23,p6281) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baselga, J. Articles by Arteaga, C. L. Search for Related Content PubMed PubMed Citation Articles by Baselga, J. Articles by Arteaga, C. L. Social Bookmarking                            What's this?

Critical Update and Emerging Trends in Epidermal Growth Factor Receptor Targeting in Cancer

José Baselga, Carlos L. Arteaga

From the Medical Oncology Service, Vall d'Hebron Research Institute and Vall d'Hebron University Hospital, Barcelona, Spain; and Departments of Medicine and Cancer Biology and Breast Cancer Program, Vanderbilt-Ingram Cancer Center, Nashville, TN

Address reprint requests to José Baselga, MD, Medical Oncology Service, Vall d'Hebron Research Institute and Vall d'Hebron University Hospital, Paseo Vall d'Hebron 119-129, Barcelona 08035, Spain; e-mail: jbaselga{at}vhebron.net.

ABSTRACT

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB receptor family that is abnormally activated in many epithelial tumors. The aberrant activation of the EGFR leads to enhanced proliferation and other tumor-promoting activities, which provide a strong rationale to target this receptor family. There are two classes of anti-EGFR agents: monoclonal antibodies (MAbs) directed at the extracellular domain of the receptor and small molecule, adenosine triphosphate–competitive inhibitors of the receptor's tyrosine kinase. Anti-EGFR MAbs have shown antitumor activity in advanced colorectal carcinoma, squamous cell carcinomas of the head and neck, non–small-cell lung cancer (NSCLC) and renal cell carcinomas. The tyrosine kinase inhibitors (TKIs) have a partially different activity profile. They are active against NSCLC, and a specific EGFR inhibitor has shown improvement in survival. Recently, mutations and amplifications of the EGFR gene have been identified in NSCLC and predict for enhanced sensitivity to anti-EGFR TKIs. In addition to specific anti-EGFR TKIs, there are broader acting inhibitors such as dual EGFR HER-2 inhibitors and combined anti-pan-ErbB and antivascular endothelial growth factor receptor inhibitors. Current research efforts are directed at selecting the optimal dose and schedule and identifying predictive factors of response and resistance beyond EGFR gene mutations and/or amplifications. Finally, there is a need for improved strategies to integrate anti-EGFR agents with conventional therapies and to explore combinations with other molecular targeted approaches including other antireceptor therapies, receptor-downstream signaling transduction inhibitors, and targeted approaches interfering with other essential drivers of cancer, such as angiogenesis.

NOTES

Supported by a Spanish Science and Technology Ministry Grant SAF2003-03818 (J.B.), a Breast Cancer Research Foundation Grant (J.B.), National Institutes of Health R01 grant CA80915 (C.L.A.), Breast Cancer Specialized Program of Research Excellence (SPORE) Grant P50 CA98131, and Vanderbilt-Ingram Comprehensive Cancer Center Support Grant P30 CA68485.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. E. Taube, G. M. Clark, J. E. Dancey, L. M. McShane, C. C. Sigman, and S. I. Gutman A Perspective on Challenges and Issues in Biomarker Development and Drug and Biomarker Codevelopment J Natl Cancer Inst, November 4, 2009; 101(21): 1453 - 1463. [Abstract] [Full Text] [PDF]

				J. Merk, J. Rolff, M. Becker, G. Leschber, and I. Fichtner Patient-derived xenografts of non-small-cell lung cancer: a pre-clinical model to evaluate adjuvant chemotherapy? Eur. J. Cardiothorac. Surg., September 1, 2009; 36(3): 454 - 459. [Abstract] [Full Text] [PDF]

				B. Markman, F. Atzori, J. Perez-Garcia, J. Tabernero, and J. Baselga Status of PI3K inhibition and biomarker development in cancer therapeutics Ann. Onc., August 27, 2009; (2009) mdp347v1. [Abstract] [Full Text] [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]

				S. DEEN, O. L. GRIFFITH, H. MASOUDI, A. GOWN, S. J.M. JONES, and S. M. WISEMAN Anaplastic Thyroid Carcinoma Exhibits Intratumoral Molecular Homogeneity for a Therapeutic Target Panel Anticancer Res, July 1, 2009; 29(7): 2437 - 2444. [Abstract] [Full Text] [PDF]

				J. R. TONRA, E. CORCORAN, D. S. DEEVI, P. STEINER, J. KEARNEY, H. LI, D. L. LUDWIG, Z. ZHU, L. WITTE, D. SURGULADZE, et al. Prioritization of EGFR/IGF-IR/VEGFR2 Combination Targeted Therapies Utilizing Cancer Models Anticancer Res, June 1, 2009; 29(6): 1999 - 2007. [Abstract] [Full Text] [PDF]

				E. A. Hirschowitz and J. R. Yannelli Immunotherapy for Lung Cancer Proceedings of the ATS, April 15, 2009; 6(2): 224 - 232. [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]

				A. J. Mutsaers, G. Francia, S. Man, C. R. Lee, J. M.L. Ebos, Y. Wu, L. Witte, S. Berry, M. Moore, and R. S. Kerbel Dose-Dependent Increases in Circulating TGF-{alpha} and Other EGFR Ligands Act As Pharmacodynamic Markers for Optimal Biological Dosing of Cetuximab and Are Tumor Independent Clin. Cancer Res., April 1, 2009; 15(7): 2397 - 2405. [Abstract] [Full Text] [PDF]

				T. P. J. Garrett, A. W. Burgess, H. K. Gan, R. B. Luwor, G. Cartwright, F. Walker, S. G. Orchard, A. H. A. Clayton, E. C. Nice, J. Rothacker, et al. Antibodies specifically targeting a locally misfolded region of tumor associated EGFR PNAS, March 31, 2009; 106(13): 5082 - 5087. [Abstract] [Full Text] [PDF]

				S. Y. Lai, P. Koppikar, S. M. Thomas, E. E. Childs, A. M. Egloff, R. R. Seethala, B. F. Branstetter, W. E. Gooding, A. Muthukrishnan, J. M. Mountz, et al. Intratumoral Epidermal Growth Factor Receptor Antisense DNA Therapy in Head and Neck Cancer: First Human Application and Potential Antitumor Mechanisms J. Clin. Oncol., March 10, 2009; 27(8): 1235 - 1242. [Abstract] [Full Text] [PDF]

				K. Al-Nedawi, B. Meehan, R. S. Kerbel, A. C. Allison, and J. Rak Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR PNAS, March 10, 2009; 106(10): 3794 - 3799. [Abstract] [Full Text] [PDF]

				P. Laurent-Puig, A. Lievre, and H. Blons Mutations and Response to Epidermal Growth Factor Receptor Inhibitors Clin. Cancer Res., February 15, 2009; 15(4): 1133 - 1139. [Abstract] [Full Text] [PDF]

				J B Arnes, L R Begin, I Stefansson, J-S Brunet, T O Nielsen, W D Foulkes, and L A Akslen Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer J. Clin. Pathol., February 1, 2009; 62(2): 139 - 146. [Abstract] [Full Text] [PDF]

				H. J.W.L. Aerts, L. Dubois, L. Perk, P. Vermaelen, G. A.M.S. van Dongen, B. G. Wouters, and P. Lambin Disparity Between In Vivo EGFR Expression and 89Zr-Labeled Cetuximab Uptake Assessed with PET J. Nucl. Med., January 1, 2009; 50(1): 123 - 131. [Abstract] [Full Text] [PDF]

				W. K. K. WU, T. T. M. TSE, J. J. Y. SUNG, Z. J. LI, L. YU, and C. H. CHO Expression of ErbB Receptors and their Cognate Ligands in Gastric and Colon Cancer Cell Lines Anticancer Res, January 1, 2009; 29(1): 229 - 234. [Abstract] [Full Text] [PDF]

				M. Peeters, T. Price, and J.-L. Van Laethem Anti-Epidermal Growth Factor Receptor Monotherapy in the Treatment of Metastatic Colorectal Cancer: Where Are We Today? Oncologist, January 1, 2009; 14(1): 29 - 39. [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]

				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]

				M. Peipp, J. J. Lammerts van Bueren, T. Schneider-Merck, W. W. K. Bleeker, M. Dechant, T. Beyer, R. Repp, P. H. C. van Berkel, T. Vink, J. G. J. van de Winkel, et al. Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells Blood, September 15, 2008; 112(6): 2390 - 2399. [Abstract] [Full Text] [PDF]

				R. Bianco, R. Rosa, V. Damiano, G. Daniele, T. Gelardi, S. Garofalo, V. Tarallo, S. De Falco, D. Melisi, R. Benelli, et al. Vascular Endothelial Growth Factor Receptor-1 Contributes to Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Cancer Cells Clin. Cancer Res., August 15, 2008; 14(16): 5069 - 5080. [Abstract] [Full Text] [PDF]

				S. T. Lee-Hoeflich, L. Crocker, E. Yao, T. Pham, X. Munroe, K. P. Hoeflich, M. X. Sliwkowski, and H. M. Stern A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy Cancer Res., July 15, 2008; 68(14): 5878 - 5887. [Abstract] [Full Text] [PDF]

				E. Ostermann, P. Garin-Chesa, K. H. Heider, M. Kalat, H. Lamche, C. Puri, D. Kerjaschki, W. J. Rettig, and G. R. Adolf Effective Immunoconjugate Therapy in Cancer Models Targeting a Serine Protease of Tumor Fibroblasts Clin. Cancer Res., July 15, 2008; 14(14): 4584 - 4592. [Abstract] [Full Text] [PDF]

				A. J. Gonzales, K. E. Hook, I. W. Althaus, P. A. Ellis, E. Trachet, A. M. Delaney, P. J. Harvey, T. A. Ellis, D. M. Amato, J. M. Nelson, et al. Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor Mol. Cancer Ther., July 1, 2008; 7(7): 1880 - 1889. [Abstract] [Full Text] [PDF]

				D. A. Mankoff, J. M. Link, H. M. Linden, L. Sundararajan, and K. A. Krohn Tumor Receptor Imaging J. Nucl. Med., June 1, 2008; 49(Suppl_2): 149S - 163S. [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]

				M. Peipp, T. Schneider-Merck, M. Dechant, T. Beyer, J. J. Lammerts van Bueren, W. K. Bleeker, P. W. H. I. Parren, J. G. J. van de Winkel, and T. Valerius Tumor Cell Killing Mechanisms of Epidermal Growth Factor Receptor (EGFR) Antibodies Are Not Affected by Lung Cancer-Associated EGFR Kinase Mutations J. Immunol., March 15, 2008; 180(6): 4338 - 4345. [Abstract] [Full Text] [PDF]

				A. Ocana and A. Pandiella Identifying Breast Cancer Druggable Oncogenic Alterations: Lessons Learned and Future Targeted Options Clin. Cancer Res., February 15, 2008; 14(4): 961 - 970. [Abstract] [Full Text] [PDF]

				R. Rosell, G. Robinet, A. Szczesna, R. Ramlau, M. Constenla, B. C. Mennecier, W. Pfeifer, K. J. O'Byrne, T. Welte, R. Kolb, et al. Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer Ann. Onc., February 1, 2008; 19(2): 362 - 369. [Abstract] [Full Text] [PDF]

				L. M. Weiner, A. S. Belldegrun, J. Crawford, A. W. Tolcher, P. Lockbaum, R. H. Arends, L. Navale, R. G. Amado, G. Schwab, and R. A. Figlin Dose and Schedule Study of Panitumumab Monotherapy in Patients with Advanced Solid Malignancies Clin. Cancer Res., January 15, 2008; 14(2): 502 - 508. [Abstract] [Full Text] [PDF]

				K. Makabe, T. Nakanishi, K. Tsumoto, Y. Tanaka, H. Kondo, M. Umetsu, Y. Sone, R. Asano, and I. Kumagai Thermodynamic Consequences of Mutations in Vernier Zone Residues of a Humanized Anti-human Epidermal Growth Factor Receptor Murine Antibody, 528 J. Biol. Chem., January 11, 2008; 283(2): 1156 - 1166. [Abstract] [Full Text] [PDF]

				G. Folprecht, J. Tabernero, C.-H. Kohne, C. Zacharchuk, L. Paz-Ares, F. Rojo, S. Quinn, E. Casado, R. Salazar, R. Abbas, et al. Phase I Pharmacokinetic/Pharmacodynamic Study of EKB-569, an Irreversible Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Combination with Irinotecan, 5-Fluorouracil, and Leucovorin (FOLFIRI) in First-Line Treatment of Patients with Metastatic Colorectal Cancer Clin. Cancer Res., January 1, 2008; 14(1): 215 - 223. [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]

				D. Ferrari and P. Foa Targeted Therapies: Cui Prodest? J. Clin. Oncol., October 10, 2007; 25(29): 4691 - 4692. [Full Text] [PDF]

				J. Kim, W. J. Jahng, D. Di Vizio, J. S. Lee, R. Jhaveri, M. A. Rubin, A. Shisheva, and M. R. Freeman The Phosphoinositide Kinase PIKfyve Mediates Epidermal Growth Factor Receptor Trafficking to the Nucleus Cancer Res., October 1, 2007; 67(19): 9229 - 9237. [Abstract] [Full Text] [PDF]

				N. D. Gross, J. O. Boyle, B. Du, V. D. Kekatpure, A. Lantowski, H. T. Thaler, B. B. Weksler, K. Subbaramaiah, and A. J. Dannenberg Inhibition of Jun NH2-Terminal Kinases Suppresses the Growth of Experimental Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., October 1, 2007; 13(19): 5910 - 5917. [Abstract] [Full Text] [PDF]

				W. Wu, M. S. O'Reilly, R. R. Langley, R. Z. Tsan, C. H. Baker, N. Bekele, X. M. Tang, A. Onn, I. J. Fidler, and R. S. Herbst Expression of epidermal growth factor (EGF)/transforming growth factor-{alpha} by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice Mol. Cancer Ther., October 1, 2007; 6(10): 2652 - 2663. [Abstract] [Full Text] [PDF]

				M. Dechant, T. Beyer, T. Schneider-Merck, W. Weisner, M. Peipp, J. G. J. van de Winkel, and T. Valerius Effector Mechanisms of Recombinant IgA Antibodies against Epidermal Growth Factor Receptor J. Immunol., September 1, 2007; 179(5): 2936 - 2943. [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]

				M. A. Socinski Antibodies to the Epidermal Growth Factor Receptor in Non Small Cell Lung Cancer: Current Status of Matuzumab and Panitumumab Clin. Cancer Res., August 1, 2007; 13(15): 4597s - 4601s. [Abstract] [Full Text] [PDF]

				A. A. Miller, D. J. Murry, K. Owzar, D. R. Hollis, L. D. Lewis, H. L. Kindler, J. L. Marshall, M. A. Villalona-Calero, M. J. Edelman, R. J. Hohl, et al. Phase I and Pharmacokinetic Study of Erlotinib for Solid Tumors in Patients With Hepatic or Renal Dysfunction: CALGB 60101 J. Clin. Oncol., July 20, 2007; 25(21): 3055 - 3060. [Abstract] [Full Text] [PDF]

				B. C. Cho, C.-K. Im, M.-S. Park, S. K. Kim, J. Chang, J. P. Park, H. J. Choi, Y. J. Kim, S.-J. Shin, J. H. Sohn, et al. Phase II Study of Erlotinib in Advanced Non-Small-Cell Lung Cancer After Failure of Gefitinib J. Clin. Oncol., June 20, 2007; 25(18): 2528 - 2533. [Abstract] [Full Text] [PDF]

				A. M. Scott, N. Tebbutt, F.-T. Lee, T. Cavicchiolo, Z. Liu, S. Gill, A. M.T. Poon, W. Hopkins, F. E. Smyth, C. Murone, et al. A Phase I Biodistribution and Pharmacokinetic Trial of Humanized Monoclonal Antibody Hu3s193 in Patients with Advanced Epithelial Cancers that Express the Lewis-Y Antigen Clin. Cancer Res., June 1, 2007; 13(11): 3286 - 3292. [Abstract] [Full Text] [PDF]

				T. Li, Y.-H. Ling, I. D. Goldman, and R. Perez-Soler Schedule-Dependent Cytotoxic Synergism of Pemetrexed and Erlotinib in Human Non-Small Cell Lung Cancer Cells Clin. Cancer Res., June 1, 2007; 13(11): 3413 - 3422. [Abstract] [Full Text] [PDF]

				P. S. Hegde, D. Rusnak, M. Bertiaux, K. Alligood, J. Strum, R. Gagnon, and T. M. Gilmer Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles Mol. Cancer Ther., May 1, 2007; 6(5): 1629 - 1640. [Abstract] [Full Text] [PDF]

				F. Y. Feng, C. A. Lopez, D. P. Normolle, S. Varambally, X. Li, P. Y. Chun, M. A. Davis, T. S. Lawrence, and M. K. Nyati Effect of Epidermal Growth Factor Receptor Inhibitor Class in the Treatment of Head and Neck Cancer with Concurrent Radiochemotherapy In vivo Clin. Cancer Res., April 15, 2007; 13(8): 2512 - 2518. [Abstract] [Full Text] [PDF]

				G. Pentheroudakis, E. Briasoulis, and N. Pavlidis Cancer of Unknown Primary Site: Missing Primary or Missing Biology? Oncologist, April 1, 2007; 12(4): 418 - 425. [Abstract] [Full Text] [PDF]

				A. M. Scott, F.-T. Lee, N. Tebbutt, R. Herbertson, S. S. Gill, Z. Liu, E. Skrinos, C. Murone, T. H. Saunder, B. Chappell, et al. A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors PNAS, March 6, 2007; 104(10): 4071 - 4076. [Abstract] [Full Text] [PDF]

				R Dziadziuszko, B Holm, B. Skov, K Osterlind, M. Sellers, W. Franklin, P. Bunn Jr, M Varella-Garcia, and F. Hirsch Epidermal growth factor receptor gene copy number and protein level are not associated with outcome of non-small-cell lung cancer patients treated with chemotherapy Ann. Onc., March 1, 2007; 18(3): 447 - 452. [Abstract] [Full Text] [PDF]

				X. Wang, S. Zhang, G. T. MacLennan, J. N. Eble, A. Lopez-Beltran, X. J. Yang, C.-X. Pan, H. Zhou, R. Montironi, and L. Cheng Epidermal Growth Factor Receptor Protein Expression and Gene Amplification in Small Cell Carcinoma of the Urinary Bladder Clin. Cancer Res., February 1, 2007; 13(3): 953 - 957. [Abstract] [Full Text] [PDF]

				I. K. Mellinghoff, T. F. Cloughesy, and P. S. Mischel PTEN-Mediated Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors Clin. Cancer Res., January 15, 2007; 13(2): 378 - 381. [Abstract] [Full Text] [PDF]

				M. Perez-Torres, M. Guix, A. Gonzalez, and C. L. Arteaga Epidermal Growth Factor Receptor (EGFR) Antibody Down-regulates Mutant Receptors and Inhibits Tumors Expressing EGFR Mutations J. Biol. Chem., December 29, 2006; 281(52): 40183 - 40192. [Abstract] [Full Text] [PDF]

				I. R Hutcheson, J. M Knowlden, H. E Jones, R. S Burmi, R. A McClelland, D. Barrow, J. M W Gee, and R. I Nicholson Inductive mechanisms limiting response to anti-epidermal growth factor receptor therapy Endocr. Relat. Cancer, December 1, 2006; 13(Supplement_1): S89 - S97. [Abstract] [Full Text] [PDF]

				Y. Wu, Z. Zhong, J. Huber, R. Bassi, B. Finnerty, E. Corcoran, H. Li, E. Navarro, P. Balderes, X. Jimenez, et al. Anti-vascular endothelial growth factor receptor-1 antagonist antibody as a therapeutic agent for cancer. Clin. Cancer Res., November 1, 2006; 12(21): 6573 - 6584. [Abstract] [Full Text] [PDF]

				H.-J. Lenz, E. Van Cutsem, S. Khambata-Ford, R. J. Mayer, P. Gold, P. Stella, B. Mirtsching, A. L. Cohn, A. W. Pippas, N. Azarnia, et al. Multicenter Phase II and Translational Study of Cetuximab in Metastatic Colorectal Carcinoma Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidines J. Clin. Oncol., October 20, 2006; 24(30): 4914 - 4921. [Abstract] [Full Text] [PDF]

				H. M. Linden, K. A. Krohn, R. B. Livingston, and D. A. Mankoff Monitoring targeted therapy: is fluorodeoxylucose uptake a marker of early response? Clin. Cancer Res., October 1, 2006; 12(19): 5608 - 5610. [Full Text] [PDF]

				M. Scaltriti and J. Baselga The epidermal growth factor receptor pathway: a model for targeted therapy. Clin. Cancer Res., September 15, 2006; 12(18): 5268 - 5272. [Abstract] [Full Text] [PDF]

				F. Rojo, J. Tabernero, J. Albanell, E. Van Cutsem, A. Ohtsu, T. Doi, W. Koizumi, K. Shirao, H. Takiuchi, S. R. Cajal, et al. Pharmacodynamic Studies of Gefitinib in Tumor Biopsy Specimens From Patients With Advanced Gastric Carcinoma J. Clin. Oncol., September 10, 2006; 24(26): 4309 - 4316. [Abstract] [Full Text] [PDF]

				W.-C. Chou, S.-F. Huang, K.-Y. Yeh, H.-M. Wang, M.-Y. Liu, J.-J. Hsieh, Y.-C. Cheung, and J. W.-C. Chang Different Responses to Gefitinib in Lung Adenocarcinoma Coexpressing Mutant- and Wild-Type Epidermal Growth Factor Receptor Genes Jpn. J. Clin. Oncol., August 1, 2006; 36(8): 523 - 526. [Abstract] [Full Text] [PDF]

				G. R. Simon, C. R. Garrett, S. C. Olson, M. Langevin, I. A. Eiseman, J. J. Mahany, C. C. Williams, R. Lush, A. Daud, P. Munster, et al. Increased Bioavailability of Intravenous Versus Oral CI-1033, a Pan erbB Tyrosine Kinase Inhibitor: Results of a Phase I Pharmacokinetic Study Clin. Cancer Res., August 1, 2006; 12(15): 4645 - 4651. [Abstract] [Full Text] [PDF]

				R. Dziadziuszko, F. R. Hirsch, M. Varella-Garcia, and P. A. Bunn Jr. Selecting Lung Cancer Patients for Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors by Immunohistochemistry and Fluorescence In situ Hybridization--Why, When, and How? Clin. Cancer Res., July 15, 2006; 12(14): 4409s - 4415s. [Abstract] [Full Text] [PDF]

				B. E. Johnson and P. A. Janne Rationale for a Phase II Trial of Pertuzumab, a HER-2 Dimerization Inhibitor, in Patients with Non-Small Cell Lung Cancer. Clin. Cancer Res., July 15, 2006; 12(14): 4436s - 4440s. [Abstract] [Full Text] [PDF]

				J. J. Bech-Serra, B. Santiago-Josefat, C. Esselens, P. Saftig, J. Baselga, J. Arribas, and F. Canals Proteomic Identification of Desmoglein 2 and Activated Leukocyte Cell Adhesion Molecule as Substrates of ADAM17 and ADAM10 by Difference Gel Electrophoresis. Mol. Cell. Biol., July 1, 2006; 26(13): 5086 - 5095. [Abstract] [Full Text] [PDF]

				Y. Yatabe, T. Hida, Y. Horio, T. Kosaka, T. Takahashi, and T. Mitsudomi A Rapid, Sensitive Assay to Detect EGFR Mutation in Small Biopsy Specimens from Lung Cancer J. Mol. Diagn., July 1, 2006; 8(3): 335 - 341. [Abstract] [Full Text] [PDF]

				R. Asano, Y. Sone, K. Makabe, K. Tsumoto, H. Hayashi, Y. Katayose, M. Unno, T. Kudo, and I. Kumagai Humanization of the Bispecific Epidermal Growth Factor Receptor x CD3 Diabody and Its Efficacy as a Potential Clinical Reagent. Clin. Cancer Res., July 1, 2006; 12(13): 4036 - 4042. [Abstract] [Full Text] [PDF]

				K. Erjala, M. Sundvall, T. T. Junttila, N. Zhang, M. Savisalo, P. Mali, J. Kulmala, J. Pulkkinen, R. Grenman, and K. Elenius Signaling via ErbB2 and ErbB3 Associates with Resistance and Epidermal Growth Factor Receptor (EGFR) Amplification with Sensitivity to EGFR Inhibitor Gefitinib in Head and Neck Squamous Cell Carcinoma Cells. Clin. Cancer Res., July 1, 2006; 12(13): 4103 - 4111. [Abstract] [Full Text] [PDF]

				J. Castillo, E. Erroba, M. J. Perugorria, M. Santamaria, D. C. Lee, J. Prieto, M. A. Avila, and C. Berasain Amphiregulin contributes to the transformed phenotype of human hepatocellular carcinoma cells. Cancer Res., June 15, 2006; 66(12): 6129 - 6138. [Abstract] [Full Text] [PDF]

				P. A. Bunn Jr., R. Dziadziuszko, M. Varella-Garcia, W. A. Franklin, S. E. Witta, K. Kelly, and F. R. Hirsch Biological Markers for Non-Small Cell Lung Cancer Patient Selection for Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy. Clin. Cancer Res., June 15, 2006; 12(12): 3652 - 3656. [Full Text] [PDF]

				C. Kollmannsberger, M. Schittenhelm, F. Honecker, J. Tillner, D. Weber, K. Oechsle, L. Kanz, and C. Bokemeyer A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC) Ann. Onc., June 1, 2006; 17(6): 1007 - 1013. [Abstract] [Full Text] [PDF]

				J. Baselga Targeting Tyrosine Kinases in Cancer: The Second Wave. Science, May 26, 2006; 312(5777): 1175 - 1178. [Abstract] [Full Text] [PDF]

				J. Baselga Is There a Role for the Irreversible Epidermal Growth Factor Receptor Inhibitor EKB-569 in the Treatment of Cancer? A Mutation-Driven Question J. Clin. Oncol., May 20, 2006; 24(15): 2225 - 2226. [Full Text] [PDF]

				E. Calvo and J. Baselga Ethnic Differences in Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors J. Clin. Oncol., May 10, 2006; 24(14): 2158 - 2163. [Abstract] [Full Text] [PDF]

				S.-W. Han, T.-Y. Kim, Y. K. Jeon, P. G. Hwang, S.-A. Im, K.-H. Lee, J. H. Kim, D.-W. Kim, D. S. Heo, N. K. Kim, et al. Optimization of Patient Selection for Gefitinib in Non-Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation Clin. Cancer Res., April 15, 2006; 12(8): 2538 - 2544. [Abstract] [Full Text] [PDF]

				T. J. Giordano, A. Y.M. Au, R. Kuick, D. G. Thomas, D. R. Rhodes, K. G. Wilhelm Jr., M. Vinco, D. E. Misek, D. Sanders, Z. Zhu, et al. Delineation, Functional Validation, and Bioinformatic Evaluation of Gene Expression in Thyroid Follicular Carcinomas with the PAX8-PPARG Translocation. Clin. Cancer Res., April 1, 2006; 12(7): 1983 - 1993. [Abstract] [Full Text] [PDF]

				J. R. Tonra, D. S. Deevi, E. Corcoran, H. Li, S. Wang, F. E. Carrick, and D. J. Hicklin Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. Clin. Cancer Res., April 1, 2006; 12(7): 2197 - 2207. [Abstract] [Full Text] [PDF]

				D. A. Reardon, J. N. Rich, H. S. Friedman, and D. D. Bigner Recent Advances in the Treatment of Malignant Astrocytoma J. Clin. Oncol., March 10, 2006; 24(8): 1253 - 1265. [Abstract] [Full Text] [PDF]

				D. N. Amin, K. Hida, D. R. Bielenberg, and M. Klagsbrun Tumor Endothelial Cells Express Epidermal Growth Factor Receptor (EGFR) but not ErbB3 and Are Responsive to EGF and to EGFR Kinase Inhibitors Cancer Res., February 15, 2006; 66(4): 2173 - 2180. [Abstract] [Full Text] [PDF]

				M. H Nelson and C. R Dolder Lapatinib: A Novel Dual Tyrosine Kinase Inhibitor with Activity in Solid Tumors Ann. Pharmacother., February 1, 2006; 40(2): 261 - 269. [Abstract] [Full Text] [PDF]

				J. P. Delord, C. Allal, M. Canal, E. Mery, P. Rochaix, I. Hennebelle, A. Pradines, E. Chatelut, R. Bugat, S. Guichard, et al. Selective inhibition of HER2 inhibits AKT signal transduction and prolongs disease-free survival in a micrometastasis model of ovarian carcinoma Ann. Onc., December 1, 2005; 16(12): 1889 - 1897. [Abstract] [Full Text] [PDF]

				B. B.Y. Ma and A. T.C. Chan In Reply J. Clin. Oncol., October 20, 2005; 23(30): 7758 - 7759. [Full Text] [PDF]

				R. Hoekstra, H. Dumez, F. A.L.M. Eskens, A. van der Gaast, A. S.T. Planting, G. de Heus, K. C. Sizer, C. Ravera, S. Vaidyanathan, C. Bucana, et al. Phase I and Pharmacologic Study of PKI166, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients with Advanced Solid Malignancies Clin. Cancer Res., October 1, 2005; 11(19): 6908 - 6915. [Abstract] [Full Text] [PDF]

				B. E. Johnson and P. A. Janne Epidermal Growth Factor Receptor Mutations in Patients with Non-Small Cell Lung Cancer Cancer Res., September 1, 2005; 65(17): 7525 - 7529. [Abstract] [Full Text] [PDF]

				H. Bonnefoi 'Small' randomised neo-adjuvant chemotherapy trials in breast cancer reporting on pathological response: more harm than good? Ann. Onc., September 1, 2005; 16(9): 1407 - 1410. [Full Text] [PDF]

				J. D. Minna, M. J. Peyton, and A. F. Gazdar Gefitinib Versus Cetuximab in Lung Cancer: Round One J Natl Cancer Inst, August 17, 2005; 97(16): 1168 - 1169. [Full Text] [PDF]