Cardiotoxicity in cancer therapeutics

Abstract

It has been increasingly recognized that cardiac disease is a comorbid condition for cancer patients that deserves special attention. Although the primary goal of cancer therapy remains to cure the life-threatening disease, it is also important to maintain the highest possible quality of life, especially since more cancer patients survive either without cancer or with cancer as a manageable, chronic disease. Cardiovascular complications of anticancer therapies have been known for quite some time, particularly with cytotoxic therapies such as anthracyclines used at higher cumulative doses and after mediastinal radiotherapy. Frequently, cancer cells are, or become by mutation, dependent on the activity of specific tyrosine kinases, which promote proliferation and survival. In addition, when tumor size reaches a critical extent, the cancer cells depend on vascularization for further growth and metastasis. The advent of targeted monoclonal antibodies and tyrosine kinase inhibitors has revolutionized the treatment of several types of malignancies. However, many of these targeted growth and survival pathways are also important for the homeostasis of non-cancerous tissue including the myocardium, and modulators may affect protein synthesis and degradation, energy production, calcium handling and tissue integrity.