Cancer-Drug Discovery and Cardiovascular Surveillance

The story of impressive evolution in treatment for chronic myeloid leukemia has taken an unexpected turn, as serious adverse cardiovascular events have occurred in patients treated with the tyrosine kinase inhibitors ponatinib and nilotinib. Targeted BCR-ABL protein kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia (CML) and have established tyrosine kinase inhibition as a model for cancer-drug discovery and therapy in general. In 2001, imatinib became the first such tyrosine kinase inhibitor therapy to be approved by the Food and Drug Administration (FDA). Initially developed as part of a series of compounds that inhibit the platelet-derived growth factor receptor, imatinib was also shown to have potency against ABL and KIT kinases. Despite imatinib's breakthrough success, more than 20% of patients are resistant to the drug. Therefore, second- and third-generation inhibitors dasatinib, ...