Tyrosine Kinase Inhibitors as Antiangiogenic Drugs in Multiple Myeloma 英文参考文献.docVIP

Pharmaceuticals 2010, 3, 1225-1231; doi:10.3390/ph3041225 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Tyrosine Kinase Inhibitors as Antiangiogenic Drugs in Multiple Myeloma Domenico Ribatti Department of Human Anatomy and Histology, University of Bari Medical School, Piazza G. Cesare, 11, Policlinico 70124, Bari, Italy; E-Mail: ribatti@anatomia.uniba.it; Tel.: +39-080-5478240; Fax: +39-080-5478310. Received: 9 March 2010; in revised form: 21 April 2010/ Accepted: 22 April 2010 / Published: 22 April 2010 Abstract: Tyrosine kinase inhibitors are a new class of anticancer drugs, that are capable of directly interacting with the catalytic site of the target enzyme and thereby inhibiting catalysis. Therapeutically useful tyrosine kinase inhibitors are not specific for a single tyrosine kinase, but rather they are selective against a limited number of tyrosine kinases. The success of imatinib-mesylate (Gleevec?) for the treatment of patients with chronic myeloid leukemia has opened a intensive search for new small molecular compounds able to target other protein tyrosine kinases involved in the malignant transformation. This review article is focused on the use of tyrosine kinase inhibitors as antiangiogenic molecules in the treatment of multiple myeloma. Keywords: angiogenesis; antiangiogenesis; multiple myeloma; tyrosine kinase inhibitors 1. Introduction Receptor tyrosine kinases (RTKs) are transmembrane proteins containing an extracellular lectin binding domain and an intracellular catalytic domain. Many of the processes involved in tumor growth, progression and metastasis are mediated by signaling molecules acting downstream from activated RTKs. Tyrosine kinase inhibitors are small molecules able to pass the plasma membrane [1]. The tyrosine kinase vascular endothelial growth factor receptors (VEGFRs) are crucial mediators in angiogenesis and stimulation of VEGFRs a