Targets of Trastuzumab

Trastuzumab (Trastuzumab) is a recombinant humanized IgG1 monoclonal antibody directed against the HER-2 receptor, a member of the epidermal growth factor receptor, a photooncogene. Overexpressed in breast tumor cells, HER-2 over-amplifies signals provided by other receptors in the HER family by forming heterodimers. The HER-2 receptor is a transmembrane tyrosine kinase receptor consisting of an extracellular ligand-binding domain, a transmembrane region, and an intracellular or cytoplasmic tyrosine kinase domain.

Activated by forming homo- or heterodimers with otherEGFR proteins, resulting in dimerization and autophosphorylation and/or transphosphorylation of specific tyrosine residues in the intracellular domain of EGFR. Further activates downstream molecular signaling cascades, such as Ras/Raf/mitogen-activated protein kinase (MAPK), phosphoinositide-kinase/Akt, and phospholipase Cγ (PLCγ)/protein kinase C (PKC) pathways, promoting cell growth and survival as well as cell cycle progression. Due to the upregulation of HER-2 in tumor cells, overactivation of these signaling pathways and abnormal cell proliferation are observed.

Trastuzumab binds to the extracellular ligand-binding domain, blocks cleavage of the HER-2 extracellular domain, induces its antibody-induced receptor downregulation, and subsequently inhibits HER-2-mediated intracellular signaling cascades. Inhibition of the MAPK and PI3K/Akt pathways results in increased cell cycle arrest and inhibits cell growth and proliferation. Trastuzumab also mediates the activation of antibody-dependent cell-mediated cytotoxicity (ADCC) by attracting immune cells, such as natural killer (NK) cells, to tumor sites that overexpress HER-2. Although the drug is extremely unlikely to induce complement-dependent cytotoxicity (CDC) when used alone, one study showed increased and synergistic efficacy against uterine serous cancer cells when combined with pertuzumab, which also had a smaller effect on CDC when used alone.

This study shows that only a combination of two cell-binding antibodies is sufficient to bind and activate the complement component 1q (C1q) required to initiate the complement cascade. Some patients with HER-2-positive breast cancer have inherent resistance to trastuzumab. Mechanisms involved in trastuzumab resistance include deficiency of phosphatase and tensin homologs and activation of phosphoinositide-kinase, as well as overexpression of other surface receptors such as insulin-like growth factor.

Trastuzumab is sold under the brand name Herceptin in China and has entered the scope of Class B medical insurance, but it may be limited to patients who meet the indications for this drug, such asThe price for patients with HER2-positive metastatic breast cancer and its adjuvant and neoadjuvant treatment or HER2-positive metastatic gastric cancer is around RMB 6,000. The original trastuzumab drug has also been launched overseas. The drug ingredients of domestic and foreign original drugs are basically the same. For specific prices and drug details, you can consult the medical consultant. There is currently no generic drug of trastuzumab on the market.