Vascular Complications of Cancer Chemotherapy

Abstract

Development of new anticancer drugs has resulted in improved mortality rates and 5-year survival rates in patients with cancer. However, many of the modern chemotherapies are associated with cardiovascular toxicities that increase cardiovascular risk in cancer patients, including hypertension, thrombosis, heart failure, cardiomyopathy, and arrhythmias. These limitations restrict treatment options and might negatively affect the management of cancer. The cardiotoxic effects of older chemotherapeutic drugs such as alkylating agents, antimetabolites, and anticancer antibiotics have been known for a while. The newer agents, such as the antiangiogenic drugs that inhibit vascular endothelial growth factor signalling are also associated with cardiovascular pathology, especially hypertension, thromboembolism, myocardial infarction, and proteinuria. Exact mechanisms by which vascular endothelial growth factor inhibitors cause these complications are unclear but impaired endothelial function, vascular and renal damage, oxidative stress, and thrombosis might be important. With increasing use of modern chemotherapies and prolonged survival of cancer patients, the incidence of cardiovascular disease in this patient population will continue to increase. Accordingly, careful assessment and management of cardiovascular risk factors in cancer patients by oncologists and cardiologists working together is essential for optimal care so that prolonged cancer survival is not at the expense of increased cardiovascular events.

On Command Drug Delivery via Cell‐Conveyed Phototherapeutics

“…TAX (as well as other taxane derivatives) is a cytotoxic agent and endothelial cells, which line blood vessels, are especially susceptible to taxane cytotoxicity at subclinical concentrations . We note that the taxanes are extremely lipophilic and primarily serum‐protein bound in circulation .…”

Recent Advances in Hypertension and Cardiovascular Toxicities With Vascular Endothelial Growth Factor Inhibition

“…VEGF inhibitors are associated with an increased incidence of various cardiovascular pathologies including hypertension, ischaemic heart disease, heart failure, QT-interval prolongation and thromboembolism (10–12). Of these, hypertension is the most commonly reported toxicity in VEGFI trials, an effect that may limit anti-cancer treatment (9,10).…”

Out of the frying pan and into the fire: damage-associated molecular patterns and cardiovascular toxicity following cancer therapy

“…189 Other studies have also looked at the usefulness of TnI and TnT as surrogate markers for myocardial damage with the use of anti-VEGF TKI chemotherapeutics. 18,190,191 Nonetheless, cardiac troponins may not be the only molecules released during cardiovascular damage after an insult such as chemotherapy or radiation. Theoretically, a wide array of circulating DAMPs could be measured in cancer patients prior to, during, and after treatment.…”

“…However, these factors, as well as traditional cardiovascular disease risk factors (obesity, dyslipidemia, insulin resistance, and tobacco use), 4,5 do not fully account for the increased incidence of cancer therapy-induced cardiovascular toxicity. 18 The main cancer therapies reported to induce cardiovascular dysfunction and disease are radiation, vascular endothelial growth factor (VEGF) inhibitors, which encompass tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib, as well as monoclonal antibodies bevacizumab and ramucirumab, human epidermal growth factor receptor type 2 (HER2) monoclonal antibody trastuzumab, and chemotherapeutic agents such as anthracyclines, platinum-based antineoplastic drugs, microtubule inhibitors, and antimetabolites. Cardiotoxicity induced by these agents could be the result of either on-target effects (e.g.…”

“…12,13 In cancer, the presence of DAMPs has been shown to be a sign of both treatment efficacy and the development of resistance. 14,15 Mechanisms of action for therapies such as chemotherapy and radiation have been proposed and reported in the literature; [16][17][18][19][20][21] however, due to the underlying goal of cancer therapy to reduce tumor size, we hypothesize that the unintentional release of DAMPs after any cancer therapeutic contributes to the development of cardiovascular disease, including hypertension. This review describes the increased prevalence of cancer therapy-induced cardiotoxicity after cancer therapy and the possible role that DAMPs play in the disease process.…”