Journal of the National Cancer Institute Advance Access originally published online on February 24, 2009
JNCI Journal of the National Cancer Institute 2009 101(5):288-290; doi:10.1093/jnci/djp034
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© Oxford University Press 2009.
NEWS |
Targeting mTOR: Something Old, Something New
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Cancer drug development is slow–a truism that holds true especially for inhibitors of the mTOR (mammalian target of rapamycin) signaling pathway. Rapamycin (sirolimus), a natural product and the original mTOR inhibitor, was first purified in 1972. Starting in 1975, National Cancer Institute investigators found that it dramatically blocked growth in most solid tumor cell lines. But anticancer work fell by the wayside and didn’t resume until the mid-1990s, using rapamycin analogues—the so-called rapalogs. Finally, in 2007, the rapalog temsirolimus won approval from the U.S. Food and Drug Administration for treating renal cell carcinoma—more than three decades after rapamycin first showed anticancer activity.
Now, activity at both pharmaceutical companies and academic labs is at a peak. Because mTOR is centrally involved in cancer cell metabolism, growth, and proliferation, "there is growing interest in targeting this pathway," said NCI investigator Phillip Dennis, M.D., Ph.D.
Interest is high even though most clinical trials
Treatment Paradox
Exploiting Addiction
Concerns and Complications
Rapamycin Versus Rapalogs