Potentially More-Effective Cancer Drug Unveiled

Researchers have developed a platinum-based anti-cancer drug that they hope will eventually replace cisplatin, which causes severe side effects and often becomes ineffective when tumor cells become resistant to it.

Cisplatin is generally believed to kill cancer cells by binding to DNA and interfering with the cell's repair mechanism, which eventually leads to cell death. Although cisplatin is an effective drug, researchers have sought second-generation compounds that have lower therapeutic doses and fewer side effects. The most common is carboplatin, which entered the U.S. market as paraplatin in 1989 for initial treatment of advanced ovarian cancer and now outranks cisplatin in sales. Paraplatin owes its lower toxicity to the dicarboxylate ligand, which slows down the degradation of carboplatin into potentially toxic derivatives. Other analogs include ammine platinum (IV) dicarboxylates, which are metabolized to form platinum (II) cisplatin analogs.

In the their paper in the December 26, 2005, issue of Inorganic Chemistry, investigators at Virginia Commonwealth University (Richmond, USA) described a trinuclear platinum compound whose cellular absorption was significantly greater than that of neutral cisplatin, as well as other multi-nuclear platinum compounds.

"In platinum antitumor chemistry our objective is to design and develop complexes acting by new mechanisms of action,” explained senior author Dr. Nicholas Farrell, professor of chemistry at Virginia Commonwealth University. "Resistance to current drugs is due to poor cellular absorption and an increased ability of the cell to process or repair the damage caused by the chemotherapeutic agent. Our novel compound was designed to overcome resistance by emphasizing new modes of DNA binding, and in the process we have found that the amount of platinum drug entering cells is increased. The effectiveness of a platinum drug in killing cells is directly related to its concentration inside the cell.”



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