What comes around goes around: The first AIDS drug to come to market was initially developed to treat cancer, and now a drug approved for AIDS is being tested in humans as an anticancer agent.
A team led by medical oncologist Phillip Dennis at the U.S. National Cancer Institute (NCI) in Bethesda, Maryland, found evidence that drugs currently used to inhibit HIV's protease enzyme might also work against cancer. In the 1 September 2007 issue of Clinical Cancer Research, Dennis and colleagues describe test tube and mouse experiments indicating that three of these drugs show activity against six different types of cancer. One, nelfinavir, proved better than the others, leading Dennis to launch a clinical trial. "The amazing thing is we moved from preclinical to clinical studies in one-and-a-half years," says Dennis. Typically, pharmaceutical companies spend 5 to 10 years testing a promising compound before moving into human trials, notes Dennis, but "repositioning" an already-approved drug takes advantage of the already abundant data on toxicity and dosage.
It was two toxic effects of protease inhibitors in HIV-infected people that led Dennis to the idea that they might work against many cancers. Dennis's lab specializes in studying a cell-signaling pathway, Akt, that's activated in many cancers. It's well established that inhibiting the Akt pathway can lead to a buildup of lipids and glucose. "We hypothesized that if we could identify drugs that elicited those toxicities, we would find a good Akt inhibitor," says Dennis. This led them to HIV protease inhibitors, which can cause patients to develop characteristic lipid deposits and hyperglycemia.
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