Preface [Hot topic:Hsp90 Molecular Chaperone Inhibitors: Opportunities and Challenges (Guest Editor: Paul Workman)]

In this issue of Current Cancer Drug Targets we are featuring a series of articles on the subject of Hsp90 Molecular Chaperone Inhibitors: Opportunities and Challenges. This is an exciting and timely topic. As tends to be the case these days in the best translational science, the biology of a hot area is still breaking at the same time as the first attempts at therapeutic exploitation are underway. This has advantages and disadvantages. On the one hand, the fastest possible translation of new science into novel therapies is to be encouraged. The potential for patient benefit can be realised more rapidly - and if the results are disappointing we need to know that quickly too so that the approach can be dropped and other interesting opportunities can be pursued. On the other hand, early entry into a new target area carries with it the risk that we may have insufficient knowledge to fully understand the system in which we are attempting to intervene therapeutically. However, on the whole, the benefits outweigh the downsides. The interdependence and mutual synergies of fundamental and translational research are illustrated very well by the example of Hsp90. The astonishing developments in the basic research on Hsp90 can help us to develop drugs acting on this target more effectively. Equally well, the natural product inhibitors of Hsp90 have proved to be invaluable tools with which to study the function of this vitally important molecular chaperone. As we continue to gain new insights into the role of Hsp90 in evolution, development, chromatin biology and epigenetics, what makes this topic particularly timely is the fact that the Phase I clinical trials with the first-in-class Hsp90 inhibitor, 17AAG, are now coming to completion. The results have proved promising enough for Phase II clinical trials to be planned. In addition, the clinical studies with 17AAG, together with the biological underpinning, have reinforced the enthusiasm of many groups to develop novel Hsp90 inhibitors. The articles in this special issue capture the sense of excitement in the Hsp90 field and the therapeutic opportunities presented by Hsp90 inhibitors. In particular these agents offer the potential of broad spectrum activity against a wide range of different tumours through their combinatorial effects on many different oncogenic proteins and pathways and their action on all of the hallmark traits of malignancy. At the same time there are many challenges ahead to realise the full therapeutic potential of Hsp90 inhibitors. It will require clinicians and scientists from many different disciplines to work together to achieve this objective. The articles in this special issue are designed to encourage this collaborative activity. I would like to thank Chloe Mayo in my office for coordinating the assembly of this special issue and John Buolamwini and his colleagues on the production side for their help and support. I would also like to thank all the contributors for their enthusiastic participation.