Tumour metabolism is currently one of the most intense areas of cancer research. Although it has long been recognized that the metabolism of cancer cells differs from that of normal cells, opportunities to therapeutically exploit these differences have only recently emerged. In our first Review, Vander Heiden discusses the therapeutic potential and limitations of this anticancer strategy, identifies promising targets and considers evidence suggesting that it may be possible to avoid toxicity resulting from unwanted effects on normal cells. Side effects, combined with potential drug dependence, limit the use of benzodiazepines — non-selective GABAA receptor-targeting agents used to treat insomnia and anxiety. Rudolph and Knoflach review the development of GABAA subtype-selective compounds with the potential to overcome these limitations that might have novel applications in the treatment of analgesia, depression, schizophrenia and stroke, as well as cognitive enhancement in Alzheimer's disease (AD). The amyloid cascade hypothesis — which proposes that the accumulation of the amyloid-β peptide is a central event in AD pathology — has dominated research in this field. However, so far all Phase III clinical trials investigating agents that reduce the production or deposition of this peptide have failed. In their Review, Karran and colleagues re-evaluate the role of amyloid-β in AD aetiology and consider the implications for future clinical trial design. Finally, in a Perspective, a group that includes representatives from industry, academia and database providers presents new guidelines for reporting information on bioactive entities in a format that promotes consistent and complete data deposition, and enables efficient data mining to aid the development of improved molecules. The authors discuss the components of the guidelines and challenges for their implementation.
