The human epidermal growth factor receptor 2 (HER-2) protein, also known as ERBB2, is encoded by the ERBB2 gene on chromosome 17q12. The HER-2 protein contains 1255 amino acids with a molecular weight of around 185 kDa. Post-translational modifications such as phosphorylation, glycosylation, and formation of disulfide bonds are crucial for HER-2 function, influencing its stability, localization, and signaling activity.
HER-2 is primarily recognized as a membrane-bound receptor tyrosine kinase, integral to the ErbB family of receptors. Functionally, HER-2 is pivotal in regulating cell growth, proliferation, and differentiation by transducing signals from extracellular growth factors. It also acts as a key player in various signaling pathways, including the PI3K/AKT and MAPK pathways, which are fundamental for cellular survival, proliferation, and migration. HER-2 is widely expressed in epithelial tissues, including the breast, ovary, lung, and gastrointestinal tract, contributing to tissue homeostasis and development. Expression of HER-2 is tightly regulated at multiple levels, involving transcriptional, translational, and post-translational mechanisms.
Dysregulation of HER-2 expression or activity is associated with various diseases, most notably cancer. HER-2 gene amplification or protein overexpression is observed in approximately 20–30% of breast cancers. Notably, HER-2 status also serves as a critical biomarker for diagnostic and prognostic purposes in breast cancer and other malignancies. HER-2 expression levels or gene amplification status are routinely assessed in tumor tissue samples to guide treatment decisions and predict patient outcomes. While HER-2 positivity is associated with a more aggressive disease course in breast cancer, it also indicates potential responsiveness to HER-2-targeted therapies.
Targeting HER-2 has also been a significant focus of therapeutic development in oncology. Monoclonal antibodies (mAbs) such as trastuzumab (Herceptin) and pertuzumab (Perjeta) have been developed to specifically target HER-2-positive cancer cells, inhibiting HER-2 signaling and inducing antibody-dependent cellular cytotoxicity (ADCC). Additionally, antibody-drug conjugates (ADCs) like ado-trastuzumab emtansine (Kadcyla) deliver cytotoxic payloads directly to HER-2-expressing cells, resulting in targeted cell death. Small molecule inhibitors, such as lapatinib and neratinib, target the intracellular kinase domain of HER-2, blocking downstream signaling pathways and inhibiting tumor growth. These FDA-approved therapies have revolutionized the treatment of HER-2-positive breast cancer, significantly improving patient outcomes and survival rates.
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Synonyms
Receptor tyrosine-protein kinase erbB-2, Metastatic lymph node gene 19 protein, Proto-oncogene Neu, Proto-oncogene c-ErbB-2, Tyrosine kinase-type cell surface receptor HER2, p185erbB2, p185, CD340, Verb b2 Erythroblastic Leukemia Viral Oncogene Homolog 2, Neuro/Glioblastoma Derived Oncogene Homolog
Research Areas
Breast Cancer, Cardiovascular, Developmental Biology, AKT Signaling, Bladder Cancer, Infectious Disease, Signal Transduction, Transcription Factors
