Trastuzumab (Herceptin, Genentech), is a medication that inhibits over expression of human epidermal growth factor receptor type 2 (HER2), which is believed to be the cause of decreased survival rates in patients with breast cancer. The drug is FDA approved. HER2 was first described two decades ago, and occurs in over 30% of breast carcinomas. Apart from the decreased survival rate that over expression of this growth factor causes, a high copy number has also been observed to induce discrepancy in chemotherapy and hormonal therapy treatments.
Action of Trastuzumab
Trastuzumab is a humanized monoclonal antibody that targets HER2. It binds to HER2 and inhibits endurance and propagation of tumors that are HER2 dependent.
- Trastuzumab has two antigen-specific sites.
- These bind to juxtamembrane portion of extracellular domain of HER2 receptor.
- This binding inhibits activation of intracellular tyrosine kinase:
- Preventing cleavage of HER2 molecule.
- Dimerization of HER2.
- The rest of Trastuzumab is an IGg molecule with Fc receptor.
- This activates the antibody dependent cell-mediated immune system.
- The HER2-Trastuzumab complex is endocytosed and tumor cell lyses.
Several mechanisms of action of Trastuzumab have been proposed. Studies in animal models of breast cancer indicate that the drug can inhibit over expression of growth factor through angiogenesis, this inducing normalization. Pertuzumab, a new antibody, has been found to be more effective since it binds further down the molecule and inhibits dimerization. Still other studies suggest that the drug has effector cells that bring about antibody-dependent cytotoxicity.
Clinical studies have been carried out and the drug is recommended for management of metastatic breast cancer that shows over expression of HER2.
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