Gemcitabine: A Critical Nucleoside for Cancer Therapy

• Type: Another Publication in an International Scientific Journal
• Date: 2012

Authors

Gesto, DS (Author) Other; Cerqueira, NMFSA (Author) FCUP; Fernandes, PA (Author) FCUP; Ramos, MJ (Author) FCUP

Journal

Title: Current Medicinal Chemistry

Vol. 19

Pages: 1076-1087

ISSN: 0929-8673

Publisher: Bentham Science

Indexing

ISI Web of Knowledge - 77 Citations

Scopus - 77 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-CSB

DOI: 10.2174/092986712799320682

Abstract (EN): Gemcitabine (dFdC, 2',2'-difluorodeoxycytidine) is a deoxycytidine nucleoside analogue of deoxycytidine in which two fluorine atoms have been inserted into the deoxyribose ring. Like other nucleoside analogues, gemcitabine is a prodrug. It is inactive in its original form, and depends on the intracellular machinery to gain pharmacological activity. What makes gemcitabine different from other nucleoside analogues is that it is actively transported across the cell membrane, it is phosphorylated more efficiently and it is eliminated at a slower rate. These differences, together with self-potentiation mechanisms, masked DNA chain termination and extensive inhibitory efficiency against several enzymes, are the source of gemcitabine's cytotoxic activity against a wide variety of tumors. This unique combination of metabolic properties and mechanistic characteristics is only found in very few other anticancer drugs, and both the FDA and the EMEA have already approved its use for clinical purposes, for the treatment of several types of tumors. In spite of the promising results associated with gemcitabine, the knowledge of its mode of action and of the enzymes it interacts with is still not fully documented. In this article we propose to review all these aspects and summarize the path of gemcitabine inside the cell.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12