— News Center —

Advances in cardiovascular toxicity due to targeted therapy

7/24/18

　　With the development of molecular biology technology, people have gained a deeper understanding of the molecular mechanism of tumor occurrence and development, and opened up the treatment targeted at tumor cell receptors, key genes and regulatory molecules, namely "targeted therapy". Since the 1980s, researchers have developed a variety of novel anti-tumor molecular targeted drugs targeting tumor proliferation and invasion and metastasis related molecules. With the clinical application of these drugs, the mortality rate of malignant tumors has gradually declined, and the survival period of tumor survivors has been significantly prolonged. Clinical observations have shown that many cancer survivors do not die from tumors, but from a variety of cardiovascular diseases caused by drug use. It has become a difficult problem for clinicians to treat patients with cardiovascular diseases or anti-tumor drug-induced cardiovascular complications, which not only brings problems such as forced termination of treatment or early replacement of treatment plans, but also reduces the quality of life of patients and shortens the survival period of patients.

　　In clinical practice, the heart and tumor are interrelated. Various malignant tumors and therapeutic drugs affect the metabolism, biochemical characteristics and structural functions of the heart in different ways, leading to the changes of cardiac structure and the changes of cardiac contractile function, which lead to the development of congestive heart failure and arrhythmia. Currently, a wide range of HER2 inhibitors, vascular endothelial growth factor (VEGF) signaling pathway inhibitors, multi-target tyrosine kinase inhibitors and other inhibitors have been widely used in clinical practice, which may lead to the occurrence of cardiac toxicity.

1. The HER2 inhibitors

　　By bead sheet resistance is targeting the human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2, HER2, also known as ErbB2) of humanized monoclonal antibodies, by the clinical application of bead sheet resistance significantly improved the prognosis of patients with positive HER2 breast cancer, however, in the application by bead sheet resistance to chemotherapy doxorubicin plus cyclophosphamide (table) of 27% will be heart failure in patients with or without symptoms of cardiac insufficiency. Trastuzumab-related cardiosampling (TRC) is the most important adverse effect of trastuzumab in clinical use. Main show is asymptomatic left ventricular ejection fraction (left ventricular ejection fraction, LVEF) falling or have symptoms of congestive heart failure (congestive heart failure, CHF). Some researchers used echocardiography to observe the CHF incidence observed in clinical trials using trastuzumab as adjuvant therapy was about 4%, while the incidence of trastuzumab was 3% in patients with advanced MBC. Studies have shown that the decrease in LVEF induced by trastuzumab in Chinese patients following monitoring instructions is reversible and well tolerated, and there is no incidence of heart failure. Therefore, it can be seen that in clinical practice, strict compliance with the application of echocardiography in the monitoring of the cardiac toxicity of trastuzumab, guiding the withdrawal of drugs and the resumption of medication, can minimize the heart failure caused by trastuzumab and improve the safety of medication.

2.VEGF signaling pathway inhibitor

　　Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis and has become an important target of anti-tumor therapy. Bevacizumab is a monoclonal antibody recombinant humanized anti-vegf, and the FDA has approved bevacizumab as a first-line treatment for metastatic colorectal cancer, metastatic breast cancer, advanced non-small-cell lung cancer and metastatic renal cell carcinoma. With the wide application of bevacizumab, the cardiotoxicity caused by bevacizumab has attracted more and more attention. Clinical studies have found that cardiac toxicity may be the most serious adverse reaction caused by bevacizumab, mainly manifested as hypertension, decreased left ventricular ejection fraction, congestive heart failure, etc.

3. Multi-target tyrosine kinase inhibitors

　　Kinase plays an important role in maintaining cardiovascular homeostasis, including vascular metabolism and cardiac regulation. Tumor hypoxia promotes angiogenesis by inducing transcription and secretion by stabilizing hypoxia induction factor (HIF), including vascular endothelial growth factor and platelet derived factor, and blocking various tyrosine kinase small-molecule inhibitors provide an important reserve for targeted therapy of tumor. Such as imatinib, chougny for, sorafenib, by inhibiting vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, stem cell factor receptor, Fins, tyrosine kinase - 3 - the samples and multiple receptor tyrosine kinase activity, has the activity of new blood vessels form, indirect inhibit the growth of tumor cells, which have the effect of anti-tumor.

4. Summary

　　With the increasing number of tumor survivors and the increasing life span of tumor patients, it has become an important problem for doctors in the field of oncology and cardiology to combine with cardiovascular diseases or cancer therapy to induce cardiovascular complications. Although the development of tumor cardiology in China is still in its infancy and belongs to an emerging discipline, China has a large population of patients, and the study of this discipline is of great significance. Before in tumor treatment is, therefore, heart function state for individual assessment, during cancer treatment, for some patients with high risk, can benefit from prevention and screening strategies, in cancer survivors treated with potential cardiovascular toxicity, should be more vigilant about cardiovascular toxicity, reduce cardiovascular toxicity evaluation threshold, completes the tumor treatment process, the whole course management for cardiac toxicity and multidisciplinary joint diagnosis and treatment.