Investment in pharmaceutical research and development (R&D) has grown substantially in recent decades, but the output in terms of new drugs has not increased. In their Analysis article, Riccaboni and colleagues explore the underlying reasons for this by examining the Pharmaceutical Industry Database (PhID), which contains R&D information for more than 28,000 compounds investigated since 1990. They conclude that the decline in pharmaceutical productivity over the past two decades is associated with an increasing focus on the development of drugs in complex high-risk research areas, such as specific cancers. Blocking tumour angiogenesis with the aim of starving tumours of nutrients has become established as a general anticancer strategy. However, as Carmeliet and Jain discuss in their Perspective, it is increasingly appreciated that normalization of irregular blood vessels in cancer and other angiogenic diseases could be important in the therapeutic effects of anti-angiogenic drugs, and that this complementary approach could provide opportunities to improve treatment outcomes. It has recently emerged that excessive production of reactive oxygen species (ROS) in the blood vessel wall has a crucial role in the pathogenesis of vascular disease. Drummond and colleagues review the mechanisms by which oxidative stress leads to cardiovascular disease and the evidence that NADPH oxidases are key generators of ROS. They discuss therapeutic strategies for selectively targeting specific isoforms of these enzymes and the potential advantages of this approach over conventional antioxidant therapies. Finally, Waldron-Lynch and Herold review the current understanding of the immunopathogenesis of type 1 diabetes and discuss the immunomodulatory therapies aiming to preserve pancreatic β-cell function that are currently under development.
