Journal Article

Cancer-Drug Discovery and Cardiovascular Surveillance

Groarke, John D, Moslehi, Javid, Cheng, Susan

2013

Overview

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, . . .

• Publisher: Massachusetts Medical Society
• Subject: Antineoplastic Agents - adverse effects / Atherosclerosis / Cancer / Cardiovascular System - drug effects / Chronic myeloid leukemia / Drug Discovery / Drug therapy / FDA approval / Fusion Proteins, bcr-abl - antagonists & inhibitors / Fusion Proteins, bcr-abl - genetics / Humans / Imidazoles - adverse effects / Imidazoles - therapeutic use / Kinases / Leukemia / Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy / Mutation / Myeloid leukemia / Patient safety / Protein Kinase Inhibitors - adverse effects / Protein Kinase Inhibitors - therapeutic use / Protein-tyrosine kinase / Protein-Tyrosine Kinases - antagonists & inhibitors / Protein-Tyrosine Kinases - genetics / Pyridazines - adverse effects / Pyridazines - therapeutic use / Pyrimidines - adverse effects / Pyrimidines - therapeutic use / Vascular Diseases - chemically induced