spacer
spacer

PDBsum entry 1yy9

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Immune system/transferase PDB id
1yy9
Jmol
Contents
Protein chains
613 a.a. *
211 a.a. *
220 a.a. *
Ligands
NDG ×2
NAG-NAG-BMA-MAN-
MAN-MAN-MAN-MAN-
MAN
NAG-NAG ×3
NAG ×3
Waters ×56
* Residue conservation analysis
PDB id:
1yy9
Name: Immune system/transferase
Title: Structure of the extracellular domain of the epidermal growt receptor in complex with the fab fragment of cetuximab/erbi c225
Structure: Epidermal growth factor receptor. Chain: a. Fragment: unp residues 25-642. Synonym: receptor tyrosine-protein kinase erbb-1. Engineered: yes. Cetuximab fab light chain. Chain: c. Engineered: yes. Cetuximab fab heavy chain.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: egfr, erbb1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_atcc_number: sf9. Mus musculus, homo sapiens. House mouse, human.
Biol. unit: Trimer (from PQS)
Resolution:
2.60Å     R-factor:   0.242     R-free:   0.289
Authors: S.Li,K.R.Schmitz,P.D.Jeffrey,J.J.W.Wiltzius,P.Kussie,K.M.Fer
Key ref:
S.Li et al. (2005). Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell, 7, 301-311. PubMed id: 15837620 DOI: 10.1016/j.ccr.2005.03.003
Date:
24-Feb-05     Release date:   26-Apr-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00533  (EGFR_HUMAN) -  Epidermal growth factor receptor
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1210 a.a.
613 a.a.*
Protein chain
No UniProt id for this chain
Struc: 211 a.a.
Protein chain
No UniProt id for this chain
Struc: 220 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.2.7.10.1  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
ATP
+
[protein]-L-tyrosine
Bound ligand (Het Group name = NDG)
matches with 47.62% similarity
= ADP
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     transmembrane receptor protein tyrosine kinase signaling pathway   2 terms 
  Biochemical function     ATP binding     2 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.ccr.2005.03.003 Cancer Cell 7:301-311 (2005)
PubMed id: 15837620  
 
 
Structural basis for inhibition of the epidermal growth factor receptor by cetuximab.
S.Li, K.R.Schmitz, P.D.Jeffrey, J.J.Wiltzius, P.Kussie, K.M.Ferguson.
 
  ABSTRACT  
 
Recent structural studies of epidermal growth factor receptor (EGFR) family extracellular regions have identified an unexpected mechanism for ligand-induced receptor dimerization that has important implications for activation and inhibition of these receptors. Here we describe the 2.8 angstroms resolution X-ray crystal structure of the antigen binding (Fab) fragment from cetuximab (Erbitux), an inhibitory anti-EGFR antibody, in complex with the soluble extracellular region of EGFR (sEGFR). The sEGFR is in the characteristic "autoinhibited" or "tethered" inactive configuration. Cetuximab interacts exclusively with domain III of sEGFR, partially occluding the ligand binding region on this domain and sterically preventing the receptor from adopting the extended conformation required for dimerization. We suggest that both these effects contribute to potent inhibition of EGFR activation.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Mechanism of ligand-induced EGFR dimerization
Figure 6.
Figure 6. Cetuximab prevents sEGFR from adopting the extended conformation
 
  The above figures are reprinted by permission from Cell Press: Cancer Cell (2005, 7, 301-311) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22218287 N.J.Bessman, and M.A.Lemmon (2012).
Finding the missing links in EGFR.
  Nat Struct Mol Biol, 19, 1-3.  
21417852 A.Burgos-Tiburcio, E.S.Santos, B.A.Arango, and L.E.Raez (2011).
Development of targeted therapy for squamous cell carcinomas of the head and neck.
  Expert Rev Anticancer Ther, 11, 373-386.  
21822280 L.Z.Mi, C.Lu, Z.Li, N.Nishida, T.Walz, and T.A.Springer (2011).
Simultaneous visualization of the extracellular and cytoplasmic domains of the epidermal growth factor receptor.
  Nat Struct Mol Biol, 18, 984-989.  
21273060 R.Krumbach, J.Schüler, M.Hofmann, T.Giesemann, H.H.Fiebig, and T.Beckers (2011).
Primary resistance to cetuximab in a panel of patient-derived tumour xenograft models: activation of MET as one mechanism for drug resistance.
  Eur J Cancer, 47, 1231-1243.  
21244375 Y.Balagula, C.Garbe, P.L.Myskowski, A.Hauschild, B.L.Rapoport, C.B.Boers-Doets, and M.E.Lacouture (2011).
Clinical presentation and management of dermatological toxicities of epidermal growth factor receptor inhibitors.
  Int J Dermatol, 50, 129-146.  
22101934 Z.Wang, P.A.Longo, M.K.Tarrant, K.Kim, S.Head, D.J.Leahy, and P.A.Cole (2011).
Mechanistic insights into the activation of oncogenic forms of EGF receptor.
  Nat Struct Mol Biol, 18, 1388-1393.  
20504227 B.Hasselbalch, U.Lassen, H.S.Poulsen, and M.T.Stockhausen (2010).
Cetuximab insufficiently inhibits glioma cell growth due to persistent EGFR downstream signaling.
  Cancer Invest, 28, 775-787.  
20514015 C.Hartmann, N.Müller, A.Blaukat, J.Koch, I.Benhar, and W.S.Wels (2010).
Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response.
  Oncogene, 29, 4517-4527.  
20551942 D.L.Wheeler, E.F.Dunn, and P.M.Harari (2010).
Understanding resistance to EGFR inhibitors-impact on future treatment strategies.
  Nat Rev Clin Oncol, 7, 493-507.  
20037743 D.R.Siwak, M.Carey, B.T.Hennessy, C.T.Nguyen, M.J.McGahren Murray, L.Nolden, and G.B.Mills (2010).
Targeting the epidermal growth factor receptor in epithelial ovarian cancer: current knowledge and future challenges.
  J Oncol, 2010, 568938.  
20739887 I.Vivanco, and I.K.Mellinghoff (2010).
Epidermal growth factor receptor inhibitors in oncology.
  Curr Opin Oncol, 22, 573-578.  
19897418 J.A.Bonner, P.M.Harari, J.Giralt, R.B.Cohen, C.U.Jones, R.K.Sur, D.Raben, J.Baselga, S.A.Spencer, J.Zhu, H.Youssoufian, E.K.Rowinsky, and K.K.Ang (2010).
Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival.
  Lancet Oncol, 11, 21-28.  
20616078 J.B.Spangler, J.R.Neil, S.Abramovitch, Y.Yarden, F.M.White, D.A.Lauffenburger, and K.D.Wittrup (2010).
Combination antibody treatment down-regulates epidermal growth factor receptor by inhibiting endosomal recycling.
  Proc Natl Acad Sci U S A, 107, 13252-13257.  
20883055 J.E.Frampton (2010).
Cetuximab: a review of its use in squamous cell carcinoma of the head and neck.
  Drugs, 70, 1987-2010.  
20709651 J.García-Foncillas, and E.Díaz-Rubio (2010).
Progress in metastatic colorectal cancer: growing role of cetuximab to optimize clinical outcome.
  Clin Transl Oncol, 12, 533-542.  
20593498 J.Ocvirk, T.Brodowicz, F.Wrba, T.E.Ciuleanu, G.Kurteva, S.Beslija, I.Koza, Z.Pápai, D.Messinger, U.Yilmaz, Z.Faluhelyi, S.Yalcin, D.Papamichael, M.Wenczl, Z.Mrsic-Krmpotic, E.Shacham-Shmueli, D.Vrbanec, R.Esser, W.Scheithauer, and C.C.Zielinski (2010).
Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial.
  World J Gastroenterol, 16, 3133-3143.  
19940007 J.Tabernero, F.Ciardiello, F.Rivera, E.Rodriguez-Braun, F.J.Ramos, E.Martinelli, M.E.Vega-Villegas, S.Roselló, S.Liebscher, O.Kisker, T.Macarulla, J.Baselga, and A.Cervantes (2010).
Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study.
  Ann Oncol, 21, 1537-1545.  
19997736 L.C.Heukamp, and R.Büttner (2010).
[Molecular diagnostics in lung carcinoma for therapy stratification]
  Pathologe, 31, 22-28.  
20594936 L.L.Krens, J.M.Baas, H.Gelderblom, and H.J.Guchelaar (2010).
Therapeutic modulation of k-ras signaling in colorectal cancer.
  Drug Discov Today, 15, 502-516.  
20414205 L.M.Weiner, R.Surana, and S.Wang (2010).
Monoclonal antibodies: versatile platforms for cancer immunotherapy.
  Nat Rev Immunol, 10, 317-327.  
  20714355 M.A.Tejani, R.B.Cohen, and R.Mehra (2010).
The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer.
  Biologics, 4, 173-185.  
20028761 M.Campoli, R.Ferris, S.Ferrone, and X.Wang (2010).
Immunotherapy of malignant disease with tumor antigen-specific monoclonal antibodies.
  Clin Cancer Res, 16, 11-20.  
20190183 M.Cardó-Vila, R.J.Giordano, R.L.Sidman, L.F.Bronk, Z.Fan, J.Mendelsohn, W.Arap, and R.Pasqualini (2010).
From combinatorial peptide selection to drug prototype (II): targeting the epidermal growth factor receptor pathway.
  Proc Natl Acad Sci U S A, 107, 5118-5123.  
20146801 M.Herreros-Villanueva, P.Muñiz, C.García-Girón, M.Cavia-Saiz, and M.J.del Corral (2010).
TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status.
  J Transl Med, 8, 15.  
20021208 M.Hollmén, and K.Elenius (2010).
Potential of ErbB4 antibodies for cancer therapy.
  Future Oncol, 6, 37-53.  
20143444 S.Siena, R.Glynne-Jones, A.Adenis, J.Thaler, P.Preusser, E.A.Aguilar, M.S.Aapro, A.H.Loos, R.Esser, and H.Wilke (2010).
Reduced incidence of infusion-related reactions in metastatic colorectal cancer during treatment with cetuximab plus irinotecan with combined corticosteroid and antihistamine premedication.
  Cancer, 116, 1827-1837.  
  21116327 W.Boland, and G.Bebb (2010).
The emerging role of nimotuzumab in the treatment of non-small cell lung cancer.
  Biologics, 4, 289-298.  
20966921 W.Pao, and J.Chmielecki (2010).
Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer.
  Nat Rev Cancer, 10, 760-774.  
  19707410 C.A.Reade, and A.K.Ganti (2009).
EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab.
  Biologics, 3, 215-224.  
  20616912 C.Aggarwal, and H.Borghaei (2009).
Rational use of cetuximab in the treatment of advanced non-small cell lung cancer.
  Onco Targets Ther, 2, 251-260.  
19782948 C.Zheng, Y.Qiu, Q.Zeng, Y.Zhang, D.Lu, D.Yang, J.Feng, and X.Yan (2009).
Endothelial CD146 is required for in vitro tumor-induced angiogenesis: the role of a disulfide bond in signaling and dimerization.
  Int J Biochem Cell Biol, 41, 2163-2172.  
19236156 E.A.Hopper-Borge, R.E.Nasto, V.Ratushny, L.M.Weiner, E.A.Golemis, and I.Astsaturov (2009).
Mechanisms of tumor resistance to EGFR-targeted therapies.
  Expert Opin Ther Targets, 13, 339-362.  
  20616896 G.Tonini, A.Calvieri, B.Vincenzi, and D.Santini (2009).
First-line targeted therapies in the treatment of metastatic colorectal cancer - role of cetuximab.
  Onco Targets Ther, 2, 73-82.  
19602593 H.J.Liao, and G.Carpenter (2009).
Cetuximab/C225-induced intracellular trafficking of epidermal growth factor receptor.
  Cancer Res, 69, 6179-6183.  
19432811 H.K.Gan, M.Lappas, D.X.Cao, A.Cvrljevdic, A.M.Scott, and T.G.Johns (2009).
Targeting a unique EGFR epitope with monoclonal antibody 806 activates NF-kappaB and initiates tumour vascular normalization.
  J Cell Mol Med, 13, 3993-4001.  
19917537 J.A.García-Sáenz, J.Sastre, and E.Díaz-Rubio García (2009).
Biomarkers and anti-EGFR therapies for KRAS wild-type metastatic colorectal cancer.
  Clin Transl Oncol, 11, 737-747.  
19390553 J.Bernier, S.M.Bentzen, and J.B.Vermorken (2009).
Molecular therapy in head and neck oncology.
  Nat Rev Clin Oncol, 6, 266-277.  
19257852 J.Morrison, S.S.Briggs, N.K.Green, C.Thoma, K.D.Fisher, S.Kehoe, and L.W.Seymour (2009).
Cetuximab retargeting of adenovirus via the epidermal growth factor receptor for treatment of intraperitoneal ovarian cancer.
  Hum Gene Ther, 20, 239-251.  
18992239 K.R.Schmitz, and K.M.Ferguson (2009).
Interaction of antibodies with ErbB receptor extracellular regions.
  Exp Cell Res, 315, 659-670.  
19169687 K.Shirao, T.Yoshino, N.Boku, K.Kato, T.Hamaguchi, H.Yasui, N.Yamamoto, Y.Tanigawara, A.Nolting, and S.Yoshino (2009).
A phase I escalating single-dose and weekly fixed-dose study of cetuximab pharmacokinetics in Japanese patients with solid tumors.
  Cancer Chemother Pharmacol, 64, 557-564.  
19296866 L.N.Johnson (2009).
Protein kinase inhibitors: contributions from structure to clinical compounds.
  Q Rev Biophys, 42, 1.  
19038249 M.A.Lemmon (2009).
Ligand-induced ErbB receptor dimerization.
  Exp Cell Res, 315, 638-648.  
19007331 M.Dougan, and G.Dranoff (2009).
Immune therapy for cancer.
  Annu Rev Immunol, 27, 83.  
19499990 M.Landriscina, A.Piscazzi, A.Fabiano, F.Maddalena, E.Costantino, A.Farese, P.Bufo, and M.Cignarelli (2009).
Targeting epidermal growth factor receptor 1 signaling in human thyroid-stimulating hormone-independent thyroid carcinoma FRO cells results in a more chemosensitive and less angiogenic phenotype.
  Thyroid, 19, 629-637.  
19730278 N.Cézé, D.Ternant, F.Piller, D.Degenne, N.Azzopardi, E.Dorval, H.Watier, T.Lecomte, and G.Paintaud (2009).
An enzyme-linked immunosorbent assay for therapeutic drug monitoring of cetuximab.
  Ther Drug Monit, 31, 597-601.  
18979096 R.J.Taylor, S.L.Chan, A.Wood, C.J.Voskens, J.S.Wolf, W.Lin, A.Chapoval, D.H.Schulze, G.Tian, and S.E.Strome (2009).
FcgammaRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck.
  Cancer Immunol Immunother, 58, 997.  
19216848 S.C.Lee, A.López-Albaitero, and R.L.Ferris (2009).
Immunotherapy of head and neck cancer using tumor antigen-specific monoclonal antibodies.
  Curr Oncol Rep, 11, 156-162.  
19289842 T.P.Garrett, A.W.Burgess, H.K.Gan, R.B.Luwor, G.Cartwright, F.Walker, S.G.Orchard, A.H.Clayton, E.C.Nice, J.Rothacker, B.Catimel, W.K.Cavenee, L.J.Old, E.Stockert, G.Ritter, T.E.Adams, P.A.Hoyne, D.Wittrup, G.Chao, J.R.Cochran, C.Luo, M.Lou, T.Huyton, Y.Xu, W.D.Fairlie, S.Yao, A.M.Scott, and T.G.Johns (2009).
Antibodies specifically targeting a locally misfolded region of tumor associated EGFR.
  Proc Natl Acad Sci U S A, 106, 5082-5087.
PDB codes: 3g5v 3g5x 3g5y 3g5z
  20065649 X.Wang, T.K.Das, S.K.Singh, and S.Kumar (2009).
Potential aggregation prone regions in biotherapeutics: A survey of commercial monoclonal antibodies.
  MAbs, 1, 254-267.  
19063696 Z.Huang, C.Brdlik, P.Jin, and H.M.Shepard (2009).
A pan-HER approach for cancer therapy: background, current status and future development.
  Expert Opin Biol Ther, 9, 97.  
18544172 A.Gonçalves, S.Esteyries, B.Taylor-Smedra, A.Lagarde, M.Ayadi, G.Monges, F.Bertucci, B.Esterni, J.R.Delpero, O.Turrini, B.Lelong, P.Viens, J.P.Borg, D.Birnbaum, S.Olschwang, and F.Viret (2008).
A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment.
  BMC Cancer, 8, 169.  
18441330 D.Arnold, T.Höhler, C.Dittrich, F.Lordick, T.Seufferlein, J.Riemann, E.Wöll, T.Herrmann, A.Zubel, and H.J.Schmoll (2008).
Cetuximab in combination with weekly 5-fluorouracil/folinic acid and oxaliplatin (FUFOX) in untreated patients with advanced colorectal cancer: a phase Ib/II study of the AIO GI Group.
  Ann Oncol, 19, 1442-1449.  
18394550 D.J.Leahy (2008).
A molecular view of anti-ErbB monoclonal antibody therapy.
  Cancer Cell, 13, 291-293.  
18644194 D.Zips, M.Krause, A.Yaromina, A.Dörfler, W.Eicheler, C.Schütze, K.Gurtner, and M.Baumann (2008).
Epidermal growth factor receptor inhibitors for radiotherapy: biological rationale and preclinical results.
  J Pharm Pharmacol, 60, 1019-1028.  
18983242 E.S.Santos, C.Perez, C.E.Donald, and L.E.Raez (2008).
Targeting important pathways in head and neck cancer: from the bench to the clinic.
  Expert Rev Anticancer Ther, 8, 1819-1835.  
18481809 J.B.Vermorken, R.S.Herbst, X.Leon, N.Amellal, and J.Baselga (2008).
Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum-based therapies.
  Cancer, 112, 2710-2719.  
18427122 J.J.Lammerts van Bueren, W.K.Bleeker, A.Brännström, A.von Euler, M.Jansson, M.Peipp, T.Schneider-Merck, T.Valerius, J.G.van de Winkel, and P.W.Parren (2008).
The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intra- and intermolecular flexibility.
  Proc Natl Acad Sci U S A, 105, 6109-6114.  
18394559 J.Schmiedel, A.Blaukat, S.Li, T.Knöchel, and K.M.Ferguson (2008).
Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization.
  Cancer Cell, 13, 365-373.
PDB codes: 3c08 3c09
  19122861 K.Kurdziel, G.Ravizzini, B.Croft, J.Tatum, P.Choyke, and H.Kobayashi (2008).
The evolving role of nuclear molecular imaging in cancer.
  Expert Opin Med Diagn, 2, 829-842.  
18573086 K.M.Ferguson (2008).
Structure-based view of epidermal growth factor receptor regulation.
  Annu Rev Biophys, 37, 353-373.  
18031935 M.Landau, and N.Ben-Tal (2008).
Dynamic equilibrium between multiple active and inactive conformations explains regulation and oncogenic mutations in ErbB receptors.
  Biochim Biophys Acta, 1785, 12-31.  
18636661 M.Moehler, C.Frings, A.Mueller, I.Gockel, C.C.Schimanski, S.Biesterfeld, P.R.Galle, and M.H.Holtmann (2008).
VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab.
  World J Gastroenterol, 14, 4156-4167.  
18585454 M.Peipp, M.Dechant, and T.Valerius (2008).
Effector mechanisms of therapeutic antibodies against ErbB receptors.
  Curr Opin Immunol, 20, 436-443.  
  18997665 R.Mehra, R.B.Cohen, and B.A.Burtness (2008).
The role of cetuximab for the treatment of squamous cell carcinoma of the head and neck.
  Clin Adv Hematol Oncol, 6, 742-750.  
18377832 R.Mehra, R.B.Cohen, and P.M.Harari (2008).
EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck.
  Curr Oncol Rep, 10, 176-184.  
18691415 R.Solmi, M.Lauriola, M.Francesconi, D.Martini, M.Voltattorni, C.Ceccarelli, G.Ugolini, G.Rosati, S.Zanotti, I.Montroni, G.Mattei, M.Taffurelli, D.Santini, F.Pezzetti, A.Ruggeri, G.Castellani, L.Guidotti, D.Coppola, and P.Strippoli (2008).
Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines.
  BMC Cancer, 8, 227.  
17890389 S.E.Webb, S.K.Roberts, S.R.Needham, C.J.Tynan, D.J.Rolfe, M.D.Winn, D.T.Clarke, R.Barraclough, and M.L.Martin-Fernandez (2008).
Single-molecule imaging and fluorescence lifetime imaging microscopy show different structures for high- and low-affinity epidermal growth factor receptors in A431 cells.
  Biophys J, 94, 803-819.  
18275813 S.Li, P.Kussie, and K.M.Ferguson (2008).
Structural basis for EGF receptor inhibition by the therapeutic antibody IMC-11F8.
  Structure, 16, 216-227.
PDB codes: 3b2u 3b2v
18033688 T.Yoshida, I.Okamoto, T.Okabe, T.Iwasa, T.Satoh, K.Nishio, M.Fukuoka, and K.Nakagawa (2008).
Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk.
  Int J Cancer, 122, 1530-1538.  
18454685 W.Ping Li, L.A.Meyer, D.A.Capretto, C.D.Sherman, and C.J.Anderson (2008).
Receptor-binding, biodistribution, and metabolism studies of 64Cu-DOTA-cetuximab, a PET-imaging agent for epidermal growth-factor receptor-positive tumors.
  Cancer Biother Radiopharm, 23, 158-171.  
18253126 Y.Akashi, I.Okamoto, T.Iwasa, T.Yoshida, M.Suzuki, E.Hatashita, Y.Yamada, T.Satoh, M.Fukuoka, K.Ono, and K.Nakagawa (2008).
Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status.
  Br J Cancer, 98, 749-755.  
17921992 B.K.Shoichet (2007).
No free energy lunch.
  Nat Biotechnol, 25, 1109-1110.  
17624800 C.Magdelaine-Beuzelin, Q.Kaas, V.Wehbi, M.Ohresser, R.Jefferis, M.P.Lefranc, and H.Watier (2007).
Structure-function relationships of the variable domains of monoclonal antibodies approved for cancer treatment.
  Crit Rev Oncol Hematol, 64, 210-225.  
17280834 C.W.Ward, M.C.Lawrence, V.A.Streltsov, T.E.Adams, and N.M.McKern (2007).
The insulin and EGF receptor structures: new insights into ligand-induced receptor activation.
  Trends Biochem Sci, 32, 129-137.  
17256054 D.Li, H.Ji, S.Zaghlul, K.McNamara, M.C.Liang, T.Shimamura, S.Kubo, M.Takahashi, L.R.Chirieac, R.F.Padera, A.M.Scott, A.A.Jungbluth, W.K.Cavenee, L.J.Old, G.D.Demetri, and K.K.Wong (2007).
Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas.
  J Clin Invest, 117, 346-352.  
17291742 F.Nimmerjahn, and J.V.Ravetch (2007).
Antibodies, Fc receptors and cancer.
  Curr Opin Immunol, 19, 239-245.  
17671639 H.Zhang, A.Berezov, Q.Wang, G.Zhang, J.Drebin, R.Murali, and M.I.Greene (2007).
ErbB receptors: from oncogenes to targeted cancer therapies.
  J Clin Invest, 117, 2051-2058.  
17697999 J.P.Dawson, Z.Bu, and M.A.Lemmon (2007).
Ligand-induced structural transitions in ErbB receptor extracellular domains.
  Structure, 15, 942-954.  
17443277 J.Thariat, G.Yildirim, K.A.Mason, A.S.Garden, L.Milas, and K.K.Ang (2007).
Combination of radiotherapy with EGFR antagonists for head and neck carcinoma.
  Int J Clin Oncol, 12, 99.  
17967298 J.Thariat, L.Milas, and K.K.Ang (2007).
Integrating radiotherapy with epidermal growth factor receptor antagonists and other molecular therapeutics for the treatment of head and neck cancer.
  Int J Radiat Oncol Biol Phys, 69, 974-984.  
17222249 M.P.Bralet, B.Paule, B.Falissard, R.Adam, and C.Guettier (2007).
Immunohistochemical variability of epidermal growth factor receptor (EGFR) in liver metastases from colonic carcinomas.
  Histopathology, 50, 210-216.  
17274834 R.Landgraf (2007).
HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks.
  Breast Cancer Res, 9, 202.  
16847455 S.Goldoni, R.A.Iozzo, P.Kay, S.Campbell, A.McQuillan, C.Agnew, J.X.Zhu, D.R.Keene, C.C.Reed, and R.V.Iozzo (2007).
A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity.
  Oncogene, 26, 368-381.  
18034592 S.K.Blick, and L.J.Scott (2007).
Cetuximab: a review of its use in squamous cell carcinoma of the head and neck and metastatic colorectal cancer.
  Drugs, 67, 2585-2607.  
18020980 V.Khazak, I.Astsaturov, I.G.Serebriiskii, and E.A.Golemis (2007).
Selective Raf inhibition in cancer therapy.
  Expert Opin Ther Targets, 11, 1587-1609.  
17309324 Y.Li, and Z.Zhu (2007).
Monoclonal antibody-based therapeutics for leukemia.
  Expert Opin Biol Ther, 7, 319-330.  
17723181 Z.Zhu (2007).
Targeted cancer therapies based on antibodies directed against epidermal growth factor receptor: status and perspectives.
  Acta Pharmacol Sin, 28, 1476-1493.  
16547140 A.Petrelli, P.Circosta, L.Granziero, M.Mazzone, A.Pisacane, S.Fenoglio, P.M.Comoglio, and S.Giordano (2006).
Ab-induced ectodomain shedding mediates hepatocyte growth factor receptor down-regulation and hampers biological activity.
  Proc Natl Acad Sci U S A, 103, 5090-5095.  
16531225 A.Sivasubramanian, G.Chao, H.M.Pressler, K.D.Wittrup, and J.J.Gray (2006).
Structural model of the mAb 806-EGFR complex using computational docking followed by computational and experimental mutagenesis.
  Structure, 14, 401-414.
PDB codes: 2exp 2exq
16428439 C.Yang, Y.Liu, M.A.Lemmon, and M.G.Kazanietz (2006).
Essential role for Rac in heregulin beta1 mitogenic signaling: a mechanism that involves epidermal growth factor receptor and is independent of ErbB4.
  Mol Cell Biol, 26, 831-842.  
17020453 I.Astsaturov, R.B.Cohen, and P.Harari (2006).
Targeting epidermal growth factor receptor signaling in the treatment of head and neck cancer.
  Expert Rev Anticancer Ther, 6, 1179-1193.  
17134359 J.Bernier (2006).
Cetuximab in the treatment of head and neck cancer.
  Expert Rev Anticancer Ther, 6, 1539-1552.  
17177598 J.C.Lee, I.Vivanco, R.Beroukhim, J.H.Huang, W.L.Feng, R.M.DeBiasi, K.Yoshimoto, J.C.King, P.Nghiemphu, Y.Yuza, Q.Xu, H.Greulich, R.K.Thomas, J.G.Paez, T.C.Peck, D.J.Linhart, K.A.Glatt, G.Getz, R.Onofrio, L.Ziaugra, R.L.Levine, S.Gabriel, T.Kawaguchi, K.O'Neill, H.Khan, L.M.Liau, S.F.Nelson, P.N.Rao, P.Mischel, R.O.Pieper, T.Cloughesy, D.J.Leahy, W.R.Sellers, C.L.Sawyers, M.Meyerson, and I.K.Mellinghoff (2006).
Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain.
  PLoS Med, 3, e485.  
16603068 J.Huang, and W.Honda (2006).
CED: a conformational epitope database.
  BMC Immunol, 7, 7.  
16929325 K.Imai, and A.Takaoka (2006).
Comparing antibody and small-molecule therapies for cancer.
  Nat Rev Cancer, 6, 714-727.  
17082181 M.Perez-Torres, M.Guix, A.Gonzalez, and C.L.Arteaga (2006).
Epidermal growth factor receptor (EGFR) antibody down-regulates mutant receptors and inhibits tumors expressing EGFR mutations.
  J Biol Chem, 281, 40183-40192.  
16835584 M.Saunders, and T.Iveson (2006).
Management of advanced colorectal cancer: state of the art.
  Br J Cancer, 95, 131-138.  
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
16947082 S.K.Chan, M.E.Hill, and W.J.Gullick (2006).
The role of the epidermal growth factor receptor in breast cancer.
  J Mammary Gland Biol Neoplasia, 11, 3.  
16706607 S.Oliveira, P.M.van Bergen en Henegouwen, G.Storm, and R.M.Schiffelers (2006).
Molecular biology of epidermal growth factor receptor inhibition for cancer therapy.
  Expert Opin Biol Ther, 6, 605-617.  
16050785 B.Burtness (2005).
The role of cetuximab in the treatment of squamous cell cancer of the head and neck.
  Expert Opin Biol Ther, 5, 1085-1093.  
16151408 G.P.Adams, and L.M.Weiner (2005).
Monoclonal antibody therapy of cancer.
  Nat Biotechnol, 23, 1147-1157.  
16106015 J.D.Minna, M.J.Peyton, and A.F.Gazdar (2005).
Gefitinib versus cetuximab in lung cancer: round one.
  J Natl Cancer Inst, 97, 1168-1169.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.