Progress on the cardiotoxicity of sunitinib: Prognostic significance, mechanism and protective therapies.

Tyrosine kinase inhibitors (TKIs) are multi-targeted anti-cancer agents effective in the treatment of renal cell carcinoma (RCC), imatinib-resistant gastrointestinal stromal tumor (GIST) and pancreatic cancer (PC). Targeting and inhibiting a wide range of oncogenically relevant receptor tyrosine kinases (RTKs), TKIs have been the golden standard treatment of several types of cancer. The cardiotoxicity of TKIs, however, has also emerged alongside their anti-cancer potencies and has attracted research attention. Over the past few years significant progress has been made in developing a deeper understanding of aspects such as extent of cardiotoxicity, prognostic implications and survival predictions, toxicological mechanisms, and potential cardioprotective therapies. In this review we focus on a typical TKI sunitinib and summarize the up-to-date knowledge of sunitinib-induced cardiac abnormalities reported in clinical studies, weighing their implications of prognostic values. We also examine recent findings in underlying mechanisms, and development of potential cardioprotective agents.