Molecular Mechanisms of Cardiotoxicity Induced by ErbB Receptor Inhibitor Cancer Therapeutics
نویسندگان
چکیده
The introduction of the so-called "targeted therapies", particularly those drugs that inhibit the activity of tyrosine kinases, has represented a remarkable progress in the treatment of cancer. Although these drugs improve survival rates in cancer, significant cardiotoxicity, manifesting as left vertricular dysfunction and/or heart failure, has emerged. The ErbB receptor tyrosine kinases are being pursued as therapeutic targets because of their important roles in normal physiology and in cancer. Besides the fact that the ErbB receptors are indispensable during development and in normal adult physiology, epidermal growth factor (EGFR) and ErbB2 in particular have been implicated in the development of many human cancers. This review focuses on the rationale for targeting members of ErbB receptor family and numerous agents that are in use for inhibiting the pathway. We summarize the current knowledge on the physiological role of ErbB signaling in the ventricle and on structural aspects of ErbB receptor activation in cancer and cardiac cells. We examine the underlying mechanisms that result in on-target or off-target cardiotoxicities of ErbB inhibitors, which can influence the design of future anticancer therapies.
منابع مشابه
Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824.
Androgen receptor plays a critical role in the development of primary as well as advanced hormone-refractory prostate cancer. Therefore, ablation of androgen receptor from prostate cancer cells is an interesting concept for developing a new therapy not only for androgen-dependent prostate cancer but also for metastatic hormone-refractory prostate cancer, for which there is no effective treatmen...
متن کاملAntitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor.
Signaling through the erbB receptor family of tyrosine kinases contributes to the proliferation, differentiation, migration, and survival of a variety of cell types. Abnormalities in members of this receptor family have been shown to play a role in oncogenesis, thus making them attractive targets for anticancer treatments. PF-00299804 is a second-generation irreversible pan-erbB receptor tyrosi...
متن کاملNeuregulin1-ErbB Signaling in Doxorubicin-Induced Cardiotoxicity
This chapter will review basic and clinical findings regarding the cardioprotective role of Neuregulin1-ErbB signaling against the cardiotoxicity of doxorubicin, a widely used chemotherapeutic agent. In 2001, The New England Journal of Medicine published the results from clinical trials in breast cancer patients using Trastuzumab, a monoclonal antibody that blocks the ErbB2 receptor. These stud...
متن کاملCytoplasmic Her2/neu immunohistochemical staining in breast cancer; From a molecular point of view
متن کامل
A journey in anthracycline-induced cardiotoxicity with emphasizing on doxorubicin: a review article
Cancer is the second leading cause of death in the United States and has become a health problem worldwide. The reported incidence of new cancer cases is estimated at 19.3 million, with a mortality rate of 10 million in the world in 2020. There are several therapeutic approaches for cancer, including chemotherapy. Chemotherapy is consuming anti-neoplastic drugs, alone or in combination. However...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 13 شماره
صفحات -
تاریخ انتشار 2012