new trends in cancer therapy targeting ion channels and transporters癌症治疗的新趋势针对离子通道和转运蛋白.pdfVIP

Pharmaceuticals 2010, 3, 1202-1224; doi:10.3390/ph3041202 OPEN ACCESS  pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review New Trends in Cancer Therapy: Targeting Ion Channels and Transporters Annarosa Arcangeli 1,2,* and Andrea Becchetti 1,2 1 Department of Experimental Pathology and Oncology, University of Florence, Italy 2 Department of Biotechnology and Biosciences, University of Milano-Bicocca, Italy * Author to whom correspondence should be addressed; E-Mail: annarosa.arcangeli@unifi.it; Tel.: +39-055-4598206; Fax: +39-055-4598900. Received: 16 February 2010; in revised form: 25 March 2010 / Accepted: 29 March 2010 / Published: 20 April 2010 Abstract: The expression and activity of different channel types mark and regulate specific stages of cancer establishment and progression. Blocking channel activity impairs the growth of some tumors, both in vitro and in vivo, which opens a new field for pharmaceutical research. However, ion channel blockers may produce serious side effects, such as cardiac arrhythmias. For instance, Kv 11.1 (hERG1) channels are aberrantly expressed in several human cancers, in which they control different aspects of the neoplastic cell behaviour. hERG 1 blockers tend to inhibit cancer growth. However they also retard the cardiac repolarization, thus lengthening the electrocardiographic QT interval, which can lead to life-threatening ventricular arrhy