How does Herceptin cause cardiotoxicity?
Cardiotoxicity of trastuzumab is considered to be the result of attenuated HER2-mediated signaling in the heart, culminating in decreased functionality of cardiac myocytes. HER2 appears to function as a compensatory mechanism acting against cardiac stress, such as anthracycline-induced cardiotoxicity.
Is Herceptin a cardiotoxic?
Similarly, final analysis from HERceptin Adjuvant trial also reported much lower rate of cardiotoxicity with 7.25% incidence of secondary cardiac endpoint (class I or II toxicity as defined by New York Heart Association) in 2-year trastuzumab group and 4.4% in 1-year trastuzumab [16].
How does Herceptin damage the heart?
During Herceptin treatment, which is recommended for one year, toxicity can cause the heart to become too weak to pump blood. All patients on Herceptin undergo regular cardiac tests, such as an echocardiogram, to look for possible heart damage.
How Herceptin works the mechanism of action?
Herceptin works by attaching itself to the HER2 receptors on the surface of breast cancer cells and blocking them from receiving growth signals. By blocking the signals, Herceptin can slow or stop the growth of the breast cancer. Herceptin is an example of an immune targeted therapy.
What is the mechanism of action for bevacizumab?
Bevacizumab acts by selectively binding circulating VEGF, thereby inhibiting the binding of VEGF to its cell surface receptors. This inhibition leads to a reduction in microvascular growth of tumor blood vessels and thus limits the blood supply to tumor tissues.
Is Herceptin cardiotoxicity reversible?
The clinical outcome is more favorable. The trastuzumab-related cardiotoxicity in patients with HER2/neu-positive breast cancer seems to be largely reversible when trastuzumab is withdrawn.
What is cardiotoxic chemotherapy?
Cardiotoxicity, or medication-induced damage to the heart muscle—e.g., heart failure (HF), structural damage, and hypertension)— is a known adverse effect of many conventional chemotherapeutic agents.
What does trastuzumab do to the heart?
One of the known side effects of the breast cancer drug trastuzumab (Herceptin) is that it can damage the heart and its ability to pump blood effectively, sometimes resulting in mild heart failure, including shortness of breath and chest pain.
Is Herceptin an aromatase inhibitors?
Drugs called aromatase inhibitors are a type of hormone therapy that doctors often use. If breast cancer cells produce large amounts of a protein called HER2, doctors can use biological therapies such as Herceptin, which target HER2.
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).
What is the mechanism of action of bevacizumab?
How does Avastin inhibit VEGF?
Avastin blocks VEGF receptor binding Avastin works by inhibiting the action of VEGF, a specific angiogenesis growth factor that binds to receptors on blood vessels and stimulates the formation of new blood vessels. By binding to VEGF, Avastin blocks VEGF receptor binding.
What are the mechanisms of action of trastuzumab?
Mechanisms of trastuzumab-mediated cardiotoxicity are still evolving. This review highlights novel discovery of DNA Topoisomerase II as a shared target for anthracycline and trastuzumab-induced cardiotoxicity and speculates on cardiac risks associated with trastuzumab and immune checkpoint-based therapies. TRASTUZUMAB AND MECHANISMS OF ACTION
How is trastuzumab related to cardiotoxicity of the myocardium?
Pathogenesis. Trastuzumab cardiotoxicity may be induced by direct binding of trastuzumab to HER2 expressed on the myocardium, leading to an insufficient compensatory mechanism. Based on these data, it can be envisioned that trastuzumab-related cardiotoxicity, occurring after anthracyclines, is a two-step process.
How are trastuzumab and anthracyclines related to heart failure?
The pivotal, randomized multicenter phase III trial by Slamon and colleagues showed that combining trastuzumab with anthracyclines caused cardiac dysfunctions and heart failures in up to 27% of HER2-positive metastatic breast cancer patients compared with less than 7% in anthracyclines only group [11].
How many women are affected by trastuzumab in adjuvant setting?
Retrospective evaluation of incidence of cardiac dysfunctions caused by trastuzumab in adjuvant setting concluded that approximately one in four women might develop left ventricular systolic dysfunctions after trastuzumab administration [12].
