What is the mechanism of trastuzumab?

What is the mechanism of trastuzumab?

As an antibody, one of the major mechanisms of trastuzumab is to attract immune cells to tumor sites that overexpress HER2, by a mechanism called antibody-dependent cellular cytotoxicity (ADCC).

How does trastuzumab inhibit HER2 activity?

Trastuzumab reduces signaling mediated by HER2 through the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) cascades. Reduced downstream signaling through these pathways induces the cyclin-dependent kinase inhibitor p27kip1, which promotes cell-cycle arrest and apoptosis [9, 10].

How does the drug Herceptin work?

Herceptin works by blocking the effects of HER2 and encouraging the immune system (the body’s natural defences) to attack and kill the cancer cells.

How does Herceptin block HER2?

Herceptin works by attaching to the HER2 protein and blocking it from receiving growth signals. Herceptin, which is given intravenously, is approved by the U.S. Food and Drug Administration (FDA) to: treat advanced-stage, HER2-positive breast cancers.

How is trastuzumab metabolized?

Trastuzumab is metabolized to peptides and amino acids. The elimination is a complex of processes in humans but is specifically mediated by epithelial cells. Trastuzumab binds to HER-2 and is metabolized intracellularly. The consequence of intracellular binding explains a dose-dependent (nonlinear) elimination.

How does trastuzumab emtansine work in the body?

Trastuzumab attaches to the HER2 proteins (also called receptors) and can stop them growing. It also helps the body’s immune system to destroy cancer cells. When the trastuzumab attaches to the proteins, it delivers emtansine directly into the breast cancer cells.

Does trastuzumab bind to EGFR?

We showed that trastuzumab did not bind EGFR and HER3, and thus did not affect the homodimerization and phosphorylation of EGFR and HER3.

Why does resistance to the trastuzumab occur?

The most intensively studied general mechanisms of trastuzumab resistance are: (1) obstacles for trastuzumab binding to HER2; (2) upregulation of HER2 downstream signaling pathways; (3) signaling through alternate pathways; and (4) failure to trigger immune-mediated mechanisms to destroy tumor cells.

Does Herceptin lower immunity?

Does trastuzumab (Herceptin) lower your immune system? Having trastuzumab (Herceptin) could mean you’re more at risk of getting coronavirus or becoming very ill if you get it. The risk is likely to be higher if you’re having it with chemotherapy. However, being fully vaccinated against Covid-19 reduces the risk.

Is Herceptin an antibody?

Herceptin is a monoclonal antibody specifically designed to target HER2 receptors, which are transmembrane receptors on both normal cells and HER2+ tumor cells. HER2 plays an important role in the signaling network that drives cell proliferation.

Why is trastuzumab given after chemotherapy?

to treat metastatic HER2-positive breast cancer to stop the cancer from growing. to treat earlier stages of HER2-positive breast cancer, either as part of a regimen with chemotherapy or alone after a chemotherapy regimen that includes an anthracycline, to reduce the risk of the breast cancer coming back (recurrence)

What is the mechanism of action of trastuzumab?

Trastuzumab — Mechanism of Action and Use in Clinical Practice. Trastuzumab, a humanized monoclonal antibody that targets HER2, is approved by the Food and Drug Administration for patients with invasive breast cancers that overexpress HER2. This review considers the mechanism of action and the use of this agent.

How does trastuzumab trigger HER2 degradation?

Trastuzumab has been proposed to trigger HER2 internalization and degradation through promoting the activity of tyrosine kinase – ubiquitin ligase c-Cbl ( Klapper et al., 2000 ). It was observed that the binding of trastuzumab to HER2 recruits c-Cbl to its docking site, Tyr 1112 where c-Cbl ubiquitinates HER2 and leads to its degradation.

What is trastuzumab (Herceptin)?

Trastuzumab (or Herceptin) was developed by Genentech Inc (San Francisco, CA, USA) as a recombinant humanized monoclonal antibody directed against the extracellular domain IV of HER2 (Carter et al., 1992 ), has served as a remarkable example of a successful targeted therapy in breast cancer.

How does trastuzumab suppress angiogenesis?

In addition, trastuzumab suppresses angiogenesis both by induction of antiangiogenic factors and repression of proangiogenic factors. It is thought that a contribution to the unregulated growth observed in cancer could be due to proteolytic cleavage of HER2/neu that results in the release of the extracellular domain.