Epidermal growth factor receptor proliferation mechanisms

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. 

Decreased epidermal proliferation is considered to be the main mechanism of action of PUVA in the treatment of psoriasis. Once excited by UVA, psoralens can react with molecular oxygen, producing reactive oxygen species that cause mitochondrial dysfunction and lead to apoptosis of skin Langerhans cells, keratinocytes, and lymphocytes [134]. PUVA further decreases epidermal cell proliferation by noncompetitively binding to epidermal growth factor receptors and directly altering the cell surface membrane. 

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