TRASTUZUMAB MECHANISM OF ACTION

Overall, Trastuzumab is a recombinant humanized monoclonal antibiotic

that selectively binds to HER-2 glycoprotein, a member of the epidermal growth

factor family of cellular receptors (EGFR). EGFR encodes its own tyrosine kinase

which, upon receptorligand binding, normally autophosphorylates the receptor

causing downstream signalling which increases proliferation, metastatic potential

and evasion of apoptosis.

So the antibody is an IgG1 kappa antibody that contains human framework

regions and murine complementarily determining regions that binds to HER-2.

HER-2 is overexpressed in about one-third of patients with breast cancer.

Trastuzumab inhibits cell-cycle progression by decreasing cells entering the S

phase of the cell cycle, leading to downregulation of HER-2 receptors on tumor

cells and decreased cell proliferation.Trastuzumab also leads to antibody dependent

cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC),

along with directly inducing apoptosis in cells overexpressing the HER-2 protein.