Her2

Human epidermal growth factor receptors ( HER , Erb B ) form a family of surface cell receptors involved in signaling that control the normal growth and differentiation of cells. These growth factors work with ligands, none of which are specific for the HER2 receptor. HER receptors exist both as monomers and as dimers (i.e., homo- or heterodimers). The Erb B protein family includes 4 membrane-bound tyrosine protein kinases: epidermal growth factor receptor ErbB-1 , ErbB-2 ( HER2 ), ErbB-3, and ErbB-4 . All of them consist of an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. The intracellular domain is responsible for binding to a variety of signaling proteins and has both ligand-dependent and ligand-independent activities. Binding of the ligand to HER1, HER3 or HER4 causes rapid dimerization of the receptor, but HER2 is the preferred dimerization partner. In addition, HER2-containing heterodimers produce intracellular signals that are significantly stronger than signals originating from other HER combinations ^{[1] [2]} . Receptor dimerization leads to autophosphorylation of tyrosine residues of the cytoplasmic domain of the protein and initiates a number of signaling pathways.

The function of HER2 is to regulate cell growth and reproduction. In a normal cell, there are two copies of the gene for this protein, in a cancer cell - much more, as a result, many molecules of the HER2 protein are located on the surface of the cancer cell, which leads to disruption of cell growth regulation. Tumors grow faster, are more aggressive and less susceptible to chemotherapy and hormone therapy ^[3] .

Mature protein consists of 1233 amino acids, a molecular weight of 137.9 kDa. Includes an extracellular domain with 7 N-glycosylation sites, a transmembrane fragment and a cytosolic domain consisting of a protein kinase site and three protein binding sites.

Amplification or increased expression of the ERBB2 gene is observed in 30% of breast cancers. Protein is associated with tumor aggressiveness and poor prognosis ^[4] . Increased expression of this protein is also observed in cancer cells of the ovary, stomach, and uterus ^[5] .

HER2 is a highly specific target in the treatment of breast cancer. Recombinant human anti-HER2 monoclonal antibody (rhuMAb-HER2, drug English. Trastuzumab rus. Trastuzumab , Herceptin) causes the rapid removal of HER2 from the cell surface, thus reducing the availability of its heterodimers and oncogenicity ^[2] .

For 2019, there are 4 tests to detect increased expression of HER2 ^[6] :

1. IHC ( Eng. ImmunoHistoChemistry ) - Immunohistochemical study (IHC)
2. FISH ( Fluorescence In Situ Hybridization ) - In situ Fluorescence Hybridization
3. SPoT-Light HER2 CISH ( English Subtraction Probe Technology Chromogenic In Situ Hybridization ) - In situ Chromogenic Hybridization
4. Inform HER2 Dual ISH test ( Inform Dual In Situ Hybridization )

Also, for such diagnostics, DNA analysis of tumor cells by PCR can be used, the advantage of the method is the possibility of using archived tumor samples stored in paraffin blocks ^[7]

• Differentiation cluster
• Mammary cancer

• Ross JS, Fletcher JA, Linette GP, et al. The Her-2 / neu gene and protein in breast cancer 2003: biomarker and target of therapy (Eng.) // Oncologist: journal. - 2003. - Vol. 8 , no. 4 . - P. 307—325 . - DOI : 10.1634 / theoncologist . 8-4-307 . - PMID 12897328 .
• Zhou BP, Hung MC Dysregulation of cellular signaling by HER2 / neu in breast cancer (Eng.) // Semin. Oncol. : journal. - 2003. - Vol. 30 , no. 5 Suppl 16 . - P. 38-48 . - DOI : 10.1053 / j.seminoncol.200.03.08.006 . - PMID 14613025 .
• Ménard S., Casalini P., Campiglio M., et al. Role of HER2 / neu in tumor progression and therapy (English) // Cell. Mol. Life Sci. : journal. - 2005. - Vol. 61 , no. 23 . - P. 2965-2978 . - DOI : 10.1007 / s00018-004-4277-7 . - PMID 15583858 .
• Becker JC, Muller-Tidow C., Serve H., et al. Role of receptor tyrosine kinases in gastric cancer: new targets for a selective therapy (Eng.) // World J. Gastroenterol. : journal. - 2006. - Vol. 12 , no. 21 . - P. 3297-3305 . - PMID 16733844 .
• Laudadio J., Quigley DI, Tubbs R., Wolff DJ HER2 testing: a review of detection methodologies and their clinical performance (Eng.) // Expert Rev. Mol. Diagn. : journal. - 2007. - Vol. 7 , no. 1 . - P. 53-64 . - DOI : 10.1586 / 14737159.7.1.53 . - PMID 17187484 .
• Bianchi F., Tagliabue E., Ménard S., Campiglio M. Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections (English) // Cell Cycle : journal. - 2007. - Vol. 6 , no. 6 . - P. 643-646 . - DOI : 10.4161 / cc.6.6.4033 . - PMID 17374991 .
• Del Bimbo, A. Accurate evaluation of HER-2 amplification in FISH images // IEEE International Conference on Imaging Systems and Techniques (IST) / A. Del Bimbo, M. Meoni, P. Pala. - 2010. - P. 407-410. - ISBN 978-1-4244-6492-0 . - DOI : 10.1109 / IST.2010.5548461 .
• Rubin, I. The Basic Biology of HER2: [ eng. ] : PDF / I. Rubin, Y. Yarden // Annals of Oncology: Journal .. - 2001. - Vol. 12, no. suppl_1 (1 March). - P. S3 – S8. - DOI : 10.1093 / annonc / 12.suppl_1.S3 . - PMID 11521719 .

• AACR Cancer Concepts: HER2 (inaccessible link) . AACR . American Association for Cancer Research. - AACR: Information on the role of HER2 in oncology. Archived on May 16, 2008.
• Anti-HER2 therapy in the treatment of breast cancer (rus.) . Association of Oncology Patients . Date of treatment March 30, 2019.
• HER2 status . BreastCancer.Org (March 9, 2019). Date of treatment March 30, 2019.
• Search Results for HER2 - Information on HER2 on the website of the non-profit organization BreastCancer.Org