Seeing Drugs Work

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Science  21 May 2004:
Vol. 304, Issue 5674, pp. 1079-1081
DOI: 10.1126/science.304.5674.1079e

Most new cancer drugs are designed to target signaling pathways critical to tumor cell growth. One of the challenges researchers face in evaluating these drugs in both preclinical and clinical settings is their limited ability to assess whether the drugs reach their molecular targets in sufficient quantities to kill the tumor cells. A potent drug may show poor efficacy in animals or patients simply because the dose, schedule, and delivery method have not been optimized.

New molecular imaging technologies may remove much of the guesswork in this important stage of drug development. Smith-Jones et al. studied a drug that induces degradation of HER2, a growth factor receptor that is aberrantly activated in certain tumors. By administering a HER2 antibody fragment labeled with 68Ga to tumor-bearing mice, they were able to measure HER2 expression—and thus drug activity—with positron emission tomography (PET). Zhang et al. used bioluminescent imaging to monitor the activity of cancer drugs that target a cyclin-dependent kinase (Cdk) by measuring the levels of a luciferase “reporter” protein whose expression level changed in response to Cdk inactivation. In principle, both imaging methods can be adapted to monitor the pharmacodynamics of a wide range of candidate drugs. — PAK

Nature Biotechnol. 10.1038/nbt968 (2004); Nature Med. 10.1038/nm1047 (2004).

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