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Diabetes Drug Dramatically Boosts Potency of Platinum Chemotherapy

type 2 diabetes to help control blood sugar levels. An estimated 5 million people in the U.S. take Avandia or a similar drug, piozitaglone, which is sold as Actos.

Both drugs work by activating PPAR-gamma, a transcription factor that functions as a master regulator of fat development in the body, a function discovered in the Spiegelman lab in 1994. Spiegelman and others observed that certain PPAR-gamma-activating compounds, called PPAR-gamma ligands, caused cancer cells to stop growing and become more mature, or differentiated. Therefore, Spiegelman and others felt it was a logical step to try PPAR-gamma ligands as cancer treatment, but several small clinical trials found rosiglitazone alone was ineffective against several cancer types.

Despite this setback, and because rosizitaglone was well-tolerated by patients compared to standard cancer drugs, Dana-Farber researchers believed it was worthwhile to try it and similar PPAR-gamma ligands in a different context, said Geoffrey Girnun, PhD, a researcher in Spiegelman's laboratory and lead author of the Cancer Cell report. "After discussing it with other Dana-Farber researchers, we decided to try these agents in combination with platinum-based drugs, and in several different cell lines, we saw positive results," said Girnun.

In addition to rosizitaglone, the scientists tested pioglitazone and an experimental compound made by Glaxo Smith Kline, combining each of them with cisplatin, carboplatin and oxalyplatin -- all commonly used chemotherapy drugs that destroy cancer cells by damaging their DNA.

When non small-cell lung cancer cell lines were treated with rosizitaglone alone, there was no effect on growth. Carboplatin alone reduced growth of the cancer cells by about 60 percent. But when both drugs were administered, cell growth was reduced by 80 percent. The drugs were also tested individually and together on ovarian cancer cell lines that normally are resistant to chemoth
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