Epidermal growth factor cell-surface receptors

The epidermal growth factor receptor 2 (HER-2) is a protein found on the surface of cells. Heterodimerization of HER-2 activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply. HER-2 is found at abnormally high levels on the surface of many types of cancer cells, which may divide excessively. Antibodies targeting HER-2 (e.g., trastuzumab) are used as antineoplastic agents. 

Mechanism of Action Ahuman epidermal growth factor that inhibits tyrosine kinases (TK) associated with transmembrane cell surface receptors found on both normal and cancer cells. One such receptor is epidermal growth factor receptor (EGFR). Therapea-tic Effect TK activity appears to be vitally important to cell proliferation and survival. Pharmacokinetics About 60% is absorbed after PO administration bioavailability is increased by food to almost 100%. Protein binding 93%. Extensively metabolized in liver. Primarily eliminated in feces minimal excretion in urine. Half-life 36 hr. 

Transforming growth factor-a-Pseudomonas aeruginosa exotoxin A 40 (TGFa-PE40, Mr = 44,960) is a recombinant fusion protein synthesized in E. co/z.127,128 The growth factor moiety binds to surface epidermal growth factor (EGF) receptors on cancerous cells and is internalized where it releases the exotoxin domain into the cytosol.128 The toxin subunit catalytically inactivates the protein synthesis machinery of the cancer cell and the cell subsequently dies.129 It is a recombinant protein intended to be an anticancer therapeutic. 

First-line chemotherapy for the treatment of metastatic breast cancer is now largely dependent on the patient s HER-2 antigen status. The HER-2 (human epidermal growth factor receptor 2) protein is overexpressed on the surface of breast cancer cells in approximately 15-25% of patients. The measurement of this protein can be performed by immunohistochemistry methods, where the degree of protein expression is denoted by negative, 1+, 2+ or 3+. As Mrs CR s has HER-2,3+ disease, this denotes strong protein overexpression. 

Ligand-mediated endocytosis targets specific cell surface receptors and these nanoparticles are internalized by a receptor-mediated endocytic pathway. Examples of targeting transferrin, folate, lectins, and epidermal growth factor receptors are contained in the literature [185-187]. 

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