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LGD-4033 boasts high selectivity when it bonds to androgen-receptive cells in the body, opting for those in muscles and bonesas a way to treat prostate cancer. It works by blocking the cells that are mutated for cancer, but at the same time blocking the activity of the normal proteins in those cells. However, it turns out that this may not be the most effective way. "The drugs that bind to the receptors that are the same as those used by cancer cells might be more of a nuisance than anything," says Thomas Süderer, head of Cancer Research UK's laboratory in Cambridge. "The binding of the drugs might not have much of an effect on cancer cells but would be harmful to normal cells." To better understand if the approach might be more effective in targeting normal cells and less likely to damage muscle cells, Dr Süderer and a team of colleagues from universities in Germany, Japan, the UK, France and Canada tested several different approaches to target these receptors. They compared the efficacy of four drugs targeting the receptor itself with the three drug combinations shown to be most effective in cancer cells against stem cells and human prostate cancer. "Overall, we found that the three drug combinations combined to the strongest degree," explains Dr Süderer. "But, in some cases, the combinations did not appear to be beneficial to breast cancer cells." One intriguing explanation comes from the way the drugs bind when made. To bind to the receptors in the body, they need to be more tightly packed together, making them less selectable in the body's immune defences. But in muscle cells, where the receptor is made in a more 'flat' structure, the drugs bind equally well. The team is now looking into how binding properties might differ between normal cells and muscle cells. These cells are thought to harbour different receptors and could be differentially affected by the drugs' effects. So, despite not being able to deliver more drugs in larger quantities at the surface, drugs targeting prostate cancer might still be able to reach the more vulnerable prostate and breast cancers, which have the greatest number of cancers. The research is funded by the UK's Institute for Cancer Research (ICR). Related Article:

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