A way of studying the action of a breast-cancer drug in the body promises to facilitate the design of molecular-targeted therapies. The new method, described in the June issue of Nature Biotechnology, should allow scientists to determine the most effective strategies for administering this and other drugs to patients.
Drugs affect the behavior of molecules in the body, but the effects of drugs cannot readily be seen at the molecular level. The drug 17-AAG (currently in phase I clinical trials) induces the degradation of the protein HER2, a cell-surface receptor that plays a role in breast cancer. Smith-Jones and colleagues wished to understand the potency and time course of 17-AAG action on HER2. They attached a positron emitter to a fragment of Herceptin, an antibody that binds HER2, so that the antibody fragment could be detected repeatedly using PET imaging technology. After injecting the antibody fragment into mice and then treating the mice with 17-AAG, they could image the disappearance of HER2 over time.
In principle, the approach can be adapted to other drugs and molecular targets. It will be useful for understanding the action of drugs and for determining optimal doses and schedules.
Peter Smith-Jones (Memorial Sloan Kettering Cancer Center, New York, USA)
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(C) Nature Biotechnology press release.
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