Epidermal growth factor (EGFR; ErbB-1 of, HER1 in humans), the cell surface receptor for members of the family of epidermal growth factor in the extracellular protein ligands.The is a member of the ErbB receptor epidermal growth factor, (EGF family receptor family of), the family of receptor tyrosine kinase that is closely related to one of 4: ErbB-1 of (), ErbB-2 of (), and ErbB-3) of HER 3 (HER2/c-neu EGFR (ErbB-4 in) 4. EGFR mutations in activity or expression, can lead to cancer. Its receptor and epidermal growth factor, has been discovered by Stanley Cohen of Vanderbilt University. Cohen, share the medicine Ritarevu~i Mr. Montalcini 1986 Nobel Prize for the discovery of growth factors.
EGFR (epidermal growth factor) includes a complete list of the body and other ligands can be present on the cell surface, activating transforming growth factor and epidermal growth factor α (TGFα) (Note, the EGFR, It is given in ErbB receptor articles) ErbB family of being activated by the binding of its specific ligands. It was not the activation of the direct ligand, or may be in a state of being activated and then, ErbB2’s are activated by heterodimerization with other members of the family as EGFR permanent. The activation by the ligand, when the growth factors, EGFR transitions from monomers inactive dimeric active homo – In addition to forming homodimers in binding of the ligand, non-preformed There was evidence dimer active that might be present in front of the binding of the ligand. To create a heterodimer active, EGFR can be used as ErbB2/Her2/neu, to pair with other members of the ErbB family of receptors. It is not clear as to whether you want to occur after the activation of the dimmer or individual, or is important for activation only this group, but there are also data indicating that there is activation group of EGFRs form.
EGFR dimerization stimulates the intracellular protein tyrosine kinase activity of the native. As a result, phosphorylation occurs multiple tyrosine (Y) residue at the C-terminal domain of the EGFR. As shown in the figure on the left, these, includes Y1173 and Y992, Y1045, Y1068, Y1148. It phospho their own – to induce activation and autophosphorylation downstream signaling protein of several other that you want to associate with the tyrosine phosphorus through SH2 binding domain. Of the JNK pathway leading to cell proliferation MAPK, Akt and Noto DNA synthesis primarily signaling proteins downstream of these starts the signaling cascade several. Such proteins regulate cell migration, a phenotype, such as growth and adhesion. Activation of the receptor is important for the innate immune response of human skin. It can be other receptors of the kinase domain of the EGFR, and are summarized in Kurosurin tyrosine residues, and can be activated in this manner.
Mutations leading to overexpression or hyperactivity (known as restriction) EGFR number of cancer, including glioblastoma multiforme cancer and lung cancer, anal is associated. In the latter case, more or less of EGFRvIII named EGFR,, specific mutation was observed frequently. Prerequisites for cancer – mutation, can lead to cell division EGFR is not controlled misregulations family and EGFR amplification or can lead to the constitutive activation epithelium including all to the can and are involved in about 30% of the cancers.Mutations. Thus, EGFR mutations have been found in several types of cancer, and is there for the purpose of extension class of anti-cancer therapy.
Determination of EGFR has led to the development of cancer therapies directed against EGFR, including cetuximab cancer.Many for therapeutic approaches gefitinib and erlotinib directed to EGFR, lung, and colon cancer, as an oncogene. Panitumumab and cetuximab are examples of inhibitors of monoclonal antibodies. However, the former is of the type IgG1, the latter type of antibody dependent cytotoxic effect IgG2 may be quite different. Monoclonal Other clinical development is matuzumab and zalutumumab nimotuzumab. Monoclonal antibody blocks the extracellular ligand binding domain. The binding site of the block, you can not signaling molecule to attach longer, and it has a tyrosine kinase activity.
Another method uses a small molecule that inhibits the EGFR tyrosine kinase on the cytoplasmic side of the receptor. The active kinase No, EGFR, can not be a prerequisite for the binding of the protein downstream adapter, to activate. For the growth of migration and tumor growth, ostensibly to stop signaling cascade within the cell that are dependent on this pathway is reduced. (The combined inhibitors of erbB2 and EGFR) in order to identify inhibitors of the EGFR family, gefitinib, lapatinib and erlotinib quantitative or small molecule kinase inhibitors.There number that is used to detect phosphorylation of protein This is an example of how a manner.
New drugs such as Tarceva and Iressa Such targeting the EGFR directly. The patient, on the basis of tissue tested on whether indicates mutations, were divided into EGFR EGFR positive and negative. EGFR positive patients, indicating a response rate of 60% impressive beyond the response to conventional chemotherapy. However, many patients develop a resistance. Major source of two resistance 2 is the MET oncogene and the T790M mutation. However, there was a consensus approach that since 2010, was adopted to fight the FDA-approved and resistance of a particular combination. Have been reported AP26113 and target the T790M mutation results before clinical.
Efficient conversion of light that is absorbed strongly by the plasmon gold nanoparticles heating the simple bioconjugation energy and suggests their use as selective photothermal agents in cancer of the target molecule. Incubated anti-epidermal growth factor receptor (EGFR) antibody conjugated gold nanoparticles, benign epithelial cells and, (HOC 3 clone 8 and HSC 313) oral squamous cell carcinoma line of two (HaCaT cells), followed by continuous visible argon It is 514 nm which gave ion laser. This may in turn cancer cells is small, more than half of the laser power, need to be killed by benign cells after incubation with anti-EGFR Au antibody conjugated nanoparticles has been found. It was observed in all cell types in the presence of nanoparticles in the energy required for four anti-EGFR/Au to kill malignant cells coupled complex photothermal destruction yet. Because Au nanoparticles, it provides a new class of selective photothermal means via the CW laser at low power.