Human Epidermal Growth Factor Receptors

• Human epidermal growth factor receptors (HER/ErbB) include 4 cell-surface membrane tyrosine kinase receptors:

  • That transmit signals overseeing normal cell growth and differentiation:

    • HER receptors occur as both monomers and dimers:

      • Homodimers

      • Heterodimers

• HER2 oncogene is a member of the human epidermal growth factor receptor family located on chromosome 17q12:

  • All 4 HER receptors are transmembrane single subunit glycoproteins:

    • That have an:

      • Extracellular ligand-binding domain

      • A transmembrane domain

      • Intracellular tyrosine kinase catalytic domain.

  • On ligand activation, the receptors dimerize forming homodimers or heterodimers:

    • This is followed by transphosphorylation which activates several intracellular signaling pathways such as:

      • Ras/mitogen-activated protein kinase pathway

      • The phosphatidylinositol 3 kinase (PI3K)/Akt pathway

      • The Janus kinase/signal transducer and activator of transcription pathway

      • The phospholipase C pathway:

        • All of this pathways ultimately affects cell proliferation, survival, motility, and adhesion.

• Ligand binding to HER1, HER3, or HER4 results in receptor dimerization:

  • Primarily with HER2 as the dimer partner.

• HER2-containing heterodimers produce stronger intracellular signals than other HER combinations:

  • Normal cells have few HER2 receptors at the cell surface leading to very few heterodimers and thus weak and easily controlled intracellular signals.

  • HER2 overexpression results in increased HER2 receptors, increased opportunity for HER2 heterodimers, stronger intracellular signals, and malignant growth.

  • There is no known ligand for HER2 receptors to form homodimers.

  • HER receptors and known HER2 antibodies are listed in Figure below:

• HER2 amplification is the primary pathway of HER2-receptor overexpression and is a major driver of tumor development and progression in about 15% to 20% of breast cancers.

  • The overexpressed HER2 receptor is a valuable therapeutic target.

    • The 2013 ASCO CAP guidelines mandate that HER2 should be evaluated in every invasive breast cancer, whether primary or recurrence, to guide therapy.

Rodrigo Arrangoiz MS, MD, FACS a surgical oncologist and is a member of Sociedad Quirúrgica S.C at the America British Cowdray Medical Center in Mexico City:

• He is an expert in the management of breast cancer.

  • If you have any questions about HER2 positive breast cancer  please fill free to contact Dr. Arrangoiz.

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

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http://www.sociedadquirurigca.com