Epidermal growth factor receptor

EGFR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IVO, 1M14, 1M17, 1MOX, 1NQL, 1XKK, 1YY9, 1Z9I, 2EB2, 2EB3, 2GS2, 2GS6, 2GS7, 2ITN, 2ITO, 2ITP, 2ITQ, 2ITT, 2ITU, 2ITV, 2ITW, 2ITY, 2ITZ, 2J5E, 2J5F, 2J6M, 2JIT, 2JIU, 2JIV, 2KS1, 2M0B, 2M20, 2RF9, 2RFD, 2RFE, 2RGP, 3B2U, 3B2V, 3BEL, 3BUO, 3C09, 3G5V, 3G5Y, 3GOP, 3GT8, 3IKA, 3LZB, 3NJP, 3OB2, 3OP0, 3P0Y, 3PFV, 3POZ, 3QWQ, 3UG1, 3UG2, 3VJN, 3VJO, 3VRP, 3VRR, 3W2O, 3W2P, 3W2Q, 3W2R, 3W2S, 3W32, 3W33, 4G5J, 4G5P, 4HJO, 4I1Z, 4I20, 4I21, 4I22, 4I23, 4I24, 4JQ7, 4JQ8, 4JR3, 4JRV, 4KRL, 4KRM, 4KRO, 4KRP, 4LI5, 4LL0, 4LQM, 4LRM, 4R3P, 4R3R, 4R5S, 4RIW, 4RIX, 4RIY, 4RJ4, 4RJ5, 4RJ6, 4RJ7, 4RJ8, 4TKS, 4WKQ, 4WRG, 4ZJV, 5CNN, 5CNO, 5CAN, 2N5S, 5CAL, 5C8M, 4UV7, 5CAV, 5CZI, 5EDQ, 5CAS, 5CAO, 5CAP, 5EM5, 5HG5, 5EDR, 5EM8, 5EDP, 5HG7, 5CAU, 5C8K, 5C8N, 5CZH, 5CAQ, 5EM6, 4UIP, 5HG9, 5EM7, 5HG8, 4ZSE, 5HIB, 5HIC, 5D41, 4WD5
Identifiers
Aliases	EGFR , ERBB, ERBB1, HER1, NISBD2, PIG61, mENA, epidermal growth factor receptor, Genes, erbB-1, ERRP
External IDs	OMIM: 131550; MGI: 95294; HomoloGene: 74545; GeneCards: EGFR; OMA:EGFR - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7p11.2 Start 55,019,017 bp [1] End 55,211,628 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 A2|11 9.41 cM Start 16,702,203 bp [2] End 16,868,158 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nipple gums gingival epithelium placenta vulva skin of hip superficial temporal artery decidua human penis mucosa of pharynx Top expressed in left lobe of liver rib Dermatocranium external carotid artery skin of abdomen conjunctival fornix hair follicle zygote phalanx of foot calvaria More reference expression data BioGPS https://ncbi.nlm.nih.gov/gene?cmd=retrieve&dopt=default&rn=1&list_uids=1956/ More reference expression data
Gene ontology Molecular function kinase activity nitric-oxide synthase regulator activity transmembrane receptor protein tyrosine kinase activity protein phosphatase binding ATP binding protein kinase activity enzyme binding MAP kinase kinase kinase activity transferase activity chromatin binding actin filament binding double-stranded DNA binding transmembrane signaling receptor activity nucleotide binding signal transducer activity identical protein binding signaling receptor binding protein tyrosine kinase activity calmodulin binding protein kinase binding phosphatidylinositol-4,5-bisphosphate 3-kinase activity protein heterodimerization activity integrin binding epidermal growth factor binding epidermal growth factor-activated receptor activity ubiquitin protein ligase binding cadherin binding virus receptor activity protein binding Cellular component cytoplasm endosome multivesicular body, internal vesicle lumen nuclear membrane membrane focal adhesion extracellular region perinuclear region of cytoplasm nucleus cell surface endoplasmic reticulum integral component of membrane Golgi apparatus early endosome membrane receptor complex plasma membrane endocytic vesicle intracellular anatomical structure AP-2 adaptor complex endosome membrane endoplasmic reticulum membrane Golgi membrane basolateral plasma membrane Shc-EGFR complex membrane raft apical plasma membrane synapse extracellular space clathrin-coated vesicle membrane integral component of plasma membrane basal plasma membrane protein-containing complex Biological process positive regulation of protein phosphorylation negative regulation of epidermal growth factor receptor signaling pathway positive regulation of MAP kinase activity protein phosphorylation cell surface receptor signaling pathway protein insertion into membrane cell population proliferation morphogenesis of an epithelial fold ossification negative regulation of protein catabolic process transmembrane receptor protein tyrosine kinase signaling pathway positive regulation of fibroblast proliferation activation of phospholipase C activity epidermis development learning or memory protein autophosphorylation positive regulation of phosphorylation cerebral cortex cell migration digestive tract morphogenesis hair follicle development phosphorylation positive regulation of epithelial cell proliferation embryonic placenta development eyelid development in camera-type eye activation of phospholipase A2 activity positive regulation of DNA replication response to UV-A regulation of peptidyl-tyrosine phosphorylation positive regulation of cell migration positive regulation of nitric oxide biosynthetic process cellular response to estradiol stimulus positive regulation of DNA repair response to stress regulation of nitric-oxide synthase activity salivary gland morphogenesis MAPK cascade cellular response to epidermal growth factor stimulus multicellular organism development regulation of cell population proliferation cell morphogenesis cellular response to amino acid stimulus signal transduction positive regulation of transcription by RNA polymerase II lung development positive regulation of synaptic transmission, glutamatergic positive regulation of ERK1 and ERK2 cascade phosphatidylinositol phosphate biosynthetic process circadian rhythm positive regulation of superoxide anion generation positive regulation of cell population proliferation positive regulation of vasoconstriction response to osmotic stress tongue development negative regulation of apoptotic process response to cobalamin liver regeneration response to calcium ion wound healing cellular response to dexamethasone stimulus negative regulation of mitotic cell cycle cellular response to growth factor stimulus hydrogen peroxide metabolic process response to oxidative stress response to lipid regulation of cell motility intracellular signal transduction response to organic cyclic compound magnesium ion homeostasis protein biosynthesis positive regulation of production of miRNAs involved in gene silencing by miRNA positive regulation of smooth muscle cell proliferation positive regulation of bone resorption midgut development positive regulation of inflammatory response liver development diterpenoid metabolic process ERBB2 signaling pathway response to estradiol positive regulation of cell growth positive regulation of prolactin secretion astrocyte activation cellular response to mechanical stimulus response to hydroxyisoflavone neuron projection morphogenesis ovulation cycle regulation of transcription by RNA polymerase II peptidyl-tyrosine phosphorylation membrane organization positive regulation of protein kinase C activity negative regulation of ERBB signaling pathway positive regulation of protein localization to plasma membrane negative regulation of cardiocyte differentiation cellular response to reactive oxygen species positive regulation of transcription, DNA-templated regulation of JNK cascade regulation of ERK1 and ERK2 cascade cellular response to cadmium ion positive regulation of NIK/NF-kappaB signaling viral entry into host cell epidermal growth factor receptor signaling pathway positive regulation of peptidyl-serine phosphorylation peptidyl-tyrosine autophosphorylation cell-cell adhesion regulation of phosphatidylinositol 3-kinase signaling positive regulation of protein kinase B signaling positive regulation of nitric oxide mediated signal transduction cell differentiation positive regulation of cyclin-dependent protein serine/threonine kinase activity negative regulation of Notch signaling pathway positive regulation of canonical Wnt signaling pathway positive regulation of G1/S transition of mitotic cell cycle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1956,https://ncbi.nlm.nih.gov/gene?cmd=retrieve&dopt=default&rn=1&list_uids=1956 1956,https://ncbi.nlm.nih.gov/gene?cmd=retrieve&dopt=default&rn=1&list_uids=1956 13649 Ensembl ENSG00000146648 ENSMUSG00000020122 UniProt P00533 Q01279 RefSeq (mRNA) NM_001346897 NM_001346898 NM_001346899 NM_001346900 NM_001346941 NM_005228 NM_201282 NM_201283 NM_201284 NM_007912 NM_207655 RefSeq (protein) NP_001333826 NP_001333827 NP_001333828 NP_001333829 NP_001333870 NP_005219 NP_958439 NP_958440 NP_958441 NP_031938 NP_997538 Location (UCSC) Chr 7: 55.02 – 55.21 Mb Chr 11: 16.7 – 16.87 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. ^[5]

The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). In many cancer types, mutations affecting EGFR expression or activity could result in cancer. ^[6]

Epidermal growth factor and its receptor was discovered by Stanley Cohen of Vanderbilt University. Cohen shared the 1986 Nobel Prize in Medicine with Rita Levi-Montalcini for their discovery of growth factors.

Deficient signaling of the EGFR and other receptor tyrosine kinases  in humans is associated with diseases such as Alzheimer's, while over-expression is associated with the development of a wide variety of tumors. Interruption of EGFR signalling, either by blocking EGFR binding sites on the extracellular domain of the receptor or by inhibiting intracellular tyrosine kinase activity, can prevent the growth of EGFR-expressing tumours and improve the patient's condition^{[ citation needed ]}.

Function

EGFR signaling cascades

Diagram of the EGF receptor highlighting important domains

Epidermal growth factor receptor (EGFR) is a transmembrane protein that is activated by binding of its specific ligands, including epidermal growth factor and transforming growth factor alpha (TGF-α). ^[7] ErbB2 has no known direct activating ligand, and may be in an activated state constitutively or become active upon heterodimerization with other family members such as EGFR. Upon activation by its growth factor ligands, EGFR undergoes a transition from an inactive monomeric form to an active homodimer. ^[8] – although there is some evidence that preformed inactive dimers may also exist before ligand binding. ^[9] In addition to forming homodimers after ligand binding, EGFR may pair with another member of the ErbB receptor family, such as ErbB2/Her2/neu, to create an activated heterodimer. There is also evidence to suggest that clusters of activated EGFRs form, although it remains unclear whether this clustering is important for activation itself or occurs subsequent to activation of individual dimers. ^[10]

EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. As a result, autophosphorylation of several tyrosine (Y) residues in the C-terminal domain of EGFR occurs. These include Y992, Y1045, Y1068, Y1148 and Y1173, as shown in the adjacent diagram. ^[11] This autophosphorylation elicits downstream activation and signaling by several other proteins that associate with the phosphorylated tyrosines through their own phosphotyrosine-binding SH2 domains. These downstream signaling proteins initiate several signal transduction cascades, principally the MAPK, Akt and JNK pathways, leading to DNA synthesis and cell proliferation. ^[12] Such proteins modulate phenotypes such as cell migration, adhesion, and proliferation. Activation of the receptor is important for the innate immune response in human skin. Additionally, the kinase domain of the EGFR can cross-phosphorylate the tyrosine residues of other receptors with which it is aggregated and thereby activate itself.

Biological roles

The EGFR is essential for ductal development of the mammary glands, ^{[13] [14] [15]} and agonists of the EGFR such as amphiregulin, TGF-α, and heregulin induce both ductal and lobuloalveolar development even in the absence of estrogen and progesterone. ^{[16] [17]}

Role in human disease

Cancer

Mutations that lead to EGFR overexpression (known as upregulation or amplification) have been associated with a number of cancers, including adenocarcinoma of the lung (40% of cases), anal cancers, ^[18] glioblastoma (50%) and epithelian tumors of the head and neck (80–100%). ^[19] These somatic mutations involving EGFR lead to its constant activation, which produces uncontrolled cell division. ^[20] In glioblastoma a specific mutation of EGFR, called EGFRvIII, is often observed. ^[21] Mutations, amplifications or misregulations of EGFR or family members are implicated in about 30% of all epithelial cancers. ^[22]

Inflammatory disease

Aberrant EGFR signaling has been implicated in psoriasis, eczema and atherosclerosis. ^{[23] [24]} However, its exact roles in these conditions are ill-defined.

Monogenic disease

A single child displaying multi-organ epithelial inflammation was found to have a homozygous loss of function mutation in the EGFR gene. The pathogenicity of the EGFR mutation was supported by in vitro experiments and functional analysis of a skin biopsy. His severe phenotype reflects many previous research findings into EGFR function. His clinical features included a papulopustular rash, dry skin, chronic diarrhoea, abnormalities of hair growth, breathing difficulties and electrolyte imbalances. ^[25]

Wound healing and fibrosis

EGFR has been shown to play a critical role in TGF-beta1 dependent fibroblast to myofibroblast differentiation. ^{[26] [27]} Aberrant persistence of myofibroblasts within tissues can lead to progressive tissue fibrosis, impairing tissue or organ function (e.g. skin hypertrophic or keloid scars, liver cirrhosis, myocardial fibrosis, chronic kidney disease).

Medical applications

Drug target

The identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR (called "EGFR inhibitors", EGFRi), including gefitinib, ^[28] erlotinib, ^[29] afatinib, brigatinib and icotinib ^{[30] [31]} for lung cancer, and cetuximab for colon cancer. More recently AstraZeneca has developed Osimertinib, a third generation tyrosine kinase inhibitor. ^{[32] [31]}

Many therapeutic approaches are aimed at the EGFR. Cetuximab and panitumumab are examples of monoclonal antibody inhibitors. However the former is of the IgG1 type, the latter of the IgG2 type; consequences on antibody-dependent cellular cytotoxicity can be quite different. ^[33] Other monoclonals in clinical development are zalutumumab, nimotuzumab, and matuzumab. The monoclonal antibodies block the extracellular ligand binding domain. With the binding site blocked, signal molecules can no longer attach there and activate the tyrosine kinase.

Another method is using small molecules to inhibit the EGFR tyrosine kinase, which is on the cytoplasmic side of the receptor. Without kinase activity, EGFR is unable to activate itself, which is a prerequisite for binding of downstream adaptor proteins. Ostensibly by halting the signaling cascade in cells that rely on this pathway for growth, tumor proliferation and migration is diminished. Gefitinib, erlotinib, brigatinib and lapatinib (mixed EGFR and ERBB2 inhibitor) are examples of small molecule kinase inhibitors.

CimaVax-EGF, an active vaccine targeting EGF as the major ligand of EGF, uses a different approach, raising antibodies against EGF itself, thereby denying EGFR-dependent cancers of a proliferative stimulus; ^[34] it is in use as a cancer therapy against non-small-cell lung carcinoma (the most common form of lung cancer) in Cuba, and is undergoing further trials for possible licensing in Japan, Europe, and the United States. ^[35]

There are several quantitative methods available that use protein phosphorylation detection to identify EGFR family inhibitors. ^[36]

New drugs such as osimertinib, gefitinib, erlotinib and brigatinib directly target the EGFR. Patients have been divided into EGFR-positive and EGFR-negative, based upon whether a tissue test shows a mutation. EGFR-positive patients have shown a 60% response rate, which exceeds the response rate for conventional chemotherapy. ^[37]

However, many patients develop resistance. Two primary sources of resistance are the T790M mutation and MET oncogene. ^[37] However, as of 2010 there was no consensus of an accepted approach to combat resistance nor FDA approval of a specific combination. Clinical trial phase II results reported for brigatinib targeting the T790M mutation, and brigatinib received Breakthrough Therapy designation status by FDA in Feb. 2015.

The most common adverse effect of EGFR inhibitors, found in more than 90% of patients, is a papulopustular rash that spreads across the face and torso; the rash's presence is correlated with the drug's antitumor effect. ^[38] In 10% to 15% of patients the effects can be serious and require treatment. ^{[39] [40]}

Some tests are aiming at predicting benefit from EGFR treatment, as Veristrat. ^[41]

Laboratory research using genetically engineered stem cells to target EGFR in mice was reported in 2014 to show promise. ^[42] EGFR is a well-established target for monoclonal antibodies and specific tyrosine kinase inhibitors. ^[43]

Target for imaging agents

Imaging agents have been developed which identify EGFR-dependent cancers using labeled EGF. ^[44] The feasibility of in vivo imaging of EGFR expression has been demonstrated in several studies. ^{[45] [46]}

It has been proposed that certain computed tomography findings such as ground-glass opacities, air bronchogram, spiculated margins, vascular convergence, and pleural retraction can predict the presence of EGFR mutation in patients with non-small cell lung cancer. ^[47]

Interactions

Epidermal growth factor receptor has been shown to interact with:

• AR, ^{[48] [49]}
• ARF4, ^[50]
• CAV1, ^[51]
• CAV3, ^[51]
• CBL, ^{[52] [53] [54] [55] [56]}
• CBLB, ^{[53] [57]}
• CBLC, ^{[58] [59]}
• CD44, ^[26]
• CDC25A, ^[60]
• CRK, ^{[57] [61]}
• CTNNB1, ^{[62] [63] [64]}
• DCN, ^{[65] [66]}
• EGF, ^{[67] [68]}
• GRB14, ^[69]
• Grb2, ^{[57] [67] [69] [70] [71] [72] [73] [74] [75] [76]}
• JAK2, ^[77]
• MUC1, ^{[78] [79]}
• NCK1, ^{[70] [80] [81]}
• NCK2 ^{[70] [82] [83]}
• PKC alpha, ^[84]
• PLCG1, ^{[52] [85]}
• PLSCR1, ^[86]
• PTPN1, ^{[87] [88]}
• PTPN11, ^{[57] [89]}
• PTPN6, ^{[89] [90]}
• PTPRK, ^[91]
• SH2D3A, ^[92]
• SH3KBP1, ^{[93] [94]}
• SHC1, ^{[57] [95]}
• SOS1, ^{[75] [96] [97]}
• Src, ^{[77] [98] [99]}
• STAT1, ^{[77] [100]}
• STAT3, ^{[77] [101]}
• STAT5A, ^{[57] [77]}
• UBC, ^{[54] [55] [102]} and
• WAS, ^[103]
• PAR2. ^[104]

In fruitflies, the epidermal growth factor receptor interacts with Spitz. ^[105]

References

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Further reading

• Carpenter G (1987). "Receptors for epidermal growth factor and other polypeptide mitogens". Annual Review of Biochemistry. 56 (1): 881–914. doi:10.1146/annurev.bi.56.070187.004313. PMID   3039909.
• Boonstra J, Rijken P, Humbel B, Cremers F, Verkleij A, van Bergen en Henegouwen P (May 1995). "The epidermal growth factor". Cell Biology International. 19 (5): 413–30. doi:10.1006/cbir.1995.1086. PMID   7640657. S2CID   20186286.
• Carpenter G (August 2000). "The EGF receptor: a nexus for trafficking and signaling". BioEssays. 22 (8): 697–707. doi:10.1002/1521-1878(200008)22:8<697::AID-BIES3>3.0.CO;2-1. PMID   10918300. S2CID   767308.
• Filardo EJ (February 2002). "Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer". The Journal of Steroid Biochemistry and Molecular Biology. 80 (2): 231–8. doi:10.1016/S0960-0760(01)00190-X. PMID   11897506. S2CID   34995614.
• Tiganis T (January 2002). "Protein tyrosine phosphatases: dephosphorylating the epidermal growth factor receptor". IUBMB Life. 53 (1): 3–14. doi: 10.1080/15216540210811 . PMID   12018405. S2CID   8376444.
• Di Fiore PP, Scita G (October 2002). "Eps8 in the midst of GTPases". The International Journal of Biochemistry & Cell Biology. 34 (10): 1178–83. doi:10.1016/S1357-2725(02)00064-X. PMID   12127568.
• Benaim G, Villalobo A (August 2002). "Phosphorylation of calmodulin. Functional implications" (PDF). European Journal of Biochemistry. 269 (15): 3619–31. doi: 10.1046/j.1432-1033.2002.03038.x . hdl:10261/79981. PMID   12153558.
• Leu TH, Maa MC (January 2003). "Functional implication of the interaction between EGF receptor and c-Src". Frontiers in Bioscience. 8 (1–3): s28–38. doi: 10.2741/980 . PMID   12456372. S2CID   20827945.
• Anderson NL, Anderson NG (November 2002). "The human plasma proteome: history, character, and diagnostic prospects". Molecular & Cellular Proteomics. 1 (11): 845–67. doi: 10.1074/mcp.R200007-MCP200 . PMID   12488461.
• Kari C, Chan TO, Rocha de Quadros M, Rodeck U (January 2003). "Targeting the epidermal growth factor receptor in cancer: apoptosis takes center stage". Cancer Research. 63 (1): 1–5. PMID   12517767.
• Bonaccorsi L, Muratori M, Carloni V, Zecchi S, Formigli L, Forti G, Baldi E (February 2003). "Androgen receptor and prostate cancer invasion". International Journal of Andrology. 26 (1): 21–5. doi:10.1046/j.1365-2605.2003.00375.x. hdl: 2158/252370 . PMID   12534934.
• Reiter J, Maihle NJ (May 2003). "Characterization and expression of novel 60-kDa and 110-kDa EGFR isoforms in human placenta". Annals of the New York Academy of Sciences. 995 (1): 39–47. Bibcode:2003NYASA.995...39R. doi:10.1111/j.1749-6632.2003.tb03208.x. PMID   12814937. S2CID   9377682.
• Adams TE, McKern NM, Ward CW (June 2004). "Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor". Growth Factors. 22 (2): 89–95. doi:10.1080/08977190410001700998. PMID   15253384. S2CID   86844427.
• Ferguson KM (November 2004). "Active and inactive conformations of the epidermal growth factor receptor". Biochemical Society Transactions. 32 (Pt 5): 742–5. doi:10.1042/BST0320742. PMID   15494003.
• Chao C, Hellmich MR (December 2004). "Bi-directional signaling between gastrointestinal peptide hormone receptors and epidermal growth factor receptor". Growth Factors. 22 (4): 261–8. doi:10.1080/08977190412331286900. PMID   15621729. S2CID   35208079.
• Carlsson J, Ren ZP, Wester K, Sundberg AL, Heldin NE, Hesselager G, Persson M, Gedda L, Tolmachev V, Lundqvist H, Blomquist E, Nistér M (March 2006). "Planning for intracavitary anti-EGFR radionuclide therapy of gliomas. Literature review and data on EGFR expression". Journal of Neuro-Oncology. 77 (1): 33–45. doi:10.1007/s11060-005-7410-z. PMID   16200342. S2CID   42293693.
• Scartozzi M, Pierantoni C, Berardi R, Antognoli S, Bearzi I, Cascinu S (April 2006). "Epidermal growth factor receptor: a promising therapeutic target for colorectal cancer". Analytical and Quantitative Cytology and Histology. 28 (2): 61–8. PMID   16637508.
• Prudkin L, Wistuba II (October 2006). "Epidermal growth factor receptor abnormalities in lung cancer. Pathogenetic and clinical implications". Annals of Diagnostic Pathology. 10 (5): 306–15. doi:10.1016/j.anndiagpath.2006.06.011. PMID   16979526.
• Ahmed SM, Salgia R (November 2006). "Epidermal growth factor receptor mutations and susceptibility to targeted therapy in lung cancer". Respirology. 11 (6): 687–92. doi:10.1111/j.1440-1843.2006.00887.x. PMID   17052295. S2CID   38429131.
• Zhang X, Chang A (March 2007). "Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer". Journal of Medical Genetics. 44 (3): 166–72. doi:10.1136/jmg.2006.046102. PMC   2598028 . PMID   17158592.
• Mellinghoff IK, Cloughesy TF, Mischel PS (January 2007). "PTEN-mediated resistance to epidermal growth factor receptor kinase inhibitors". Clinical Cancer Research. 13 (2 Pt 1): 378–81. doi:10.1158/1078-0432.CCR-06-1992. PMID   17255257. S2CID   15077838.
• Nakamura JL (April 2007). "The epidermal growth factor receptor in malignant gliomas: pathogenesis and therapeutic implications". Expert Opinion on Therapeutic Targets. 11 (4): 463–72. doi:10.1517/14728222.11.4.463. PMID   17373877. S2CID   21947310.

External links

• Epidermal Growth Factor Receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt : P00533 (Human Epidermal growth factor receptor) at the PDBe-KB .