A CRITICAL ANALYSIS OF THE EFFECTS OF SUNITINIB ON CARDIAC CELL METABOLISM

Abstract

Abstract:

Introduction: Despite improvements in progress of survival of patients with haematological and solid malignancies by using targeted therapy with tyrosine kinase inhibitors (TKI), there are several incidences of toxicity. These include cardiotoxicity manifesting as cardiac dysfunction or damage to cardiac tissue which manifest as hypertension, acute coronary syndrome and myocardial infarction. Sunitinib is one of the TKIs approved as first-line treatment of advanced renal cell carcinoma and imatinib-resistant or intolerant gastrointestinal stromal tumors, and the anticancer therapeutic application is hampered by its cardiotoxic effect. The aim of this project is to critically analyse key studies in this area to determine whether sunitinib produced cardiotoxicity via detrimental effects on mitochondrial function. Method: The critical analysis was conducted on 6 papers out of 28 selected articles by searching on PubMed and Ovid MEDLINE by using different search keywords such as “sunitinib and cardiotoxicity, oxidative stress, reactive oxygen species(ROS) or mitochondrial dysfunction”. Critical analysis: During the analysis of 6 selected papers, it was established that multifactorial mechanisms are involved in the pathogenesis sunitinib induced cardiotoxicity, supporting the hypothesis that the alteration of mitochondrial function results in cardiac cell damage. Furthermore, it was established that sunitinib results into mitochondrial oxidative stress via generation of ROS implicated in the pathogenesis of sunitinib-induced cardiotoxicity.

Conclusion: Strong evidence was provided to support the hypothesis that mitochondrial oxidative stress results in cardiomyocyte injury. This critical analysis proffers the evidence for the role of oxidative stress in sunitinib-induced cardiotoxicity. Further, the study warrants the investigation of oxidative stress in sunitinib-induced cardiotoxicity in clinical settings.