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New agents in clinical oncology

School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PT, UK

Correspondence: K Williams, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PT, UK. E-mail: kaye.williams{at}manchester.ac.uk

Over the past few years, there have been considerable advances in our understanding of the molecular pathways and micro-environmental conditions that underpin cancer cell survival and treatment resistance. These studies have facilitated the development of a range of new agents that target specific cancer-associated pathways, processes or tumour-specific environmental conditions. Many of these new agents are not designed to be used as stand-alone therapies, but rather in combination with standard treatments to improve overall response. In addition, depending on the precise mode of action, there is also the added potential benefit of more "molecularly" targeted agents having reduced side-effects, thereby enabling an improved therapeutic index.

In November 2006, Dr Stewart Martin and I had the pleasure of organizing a 1-day scientific meeting on behalf of the British Institute of Radiology's Radiation and Cancer Biology Committee. The title of the meeting was "New Agents in Clinical Oncology" and it aimed to showcase of some of the most promising new agents that have recently entered clinical trials and to provide a forum for the presentation of exciting new pre-clinical data on their potential successors.

This special issue of the British Journal of Radiology contains review and research articles based upon selected presentations made at the meeting. Consistent with our remit for the meeting, the papers cover diverse therapeutic strategies. Two papers present data on the use of small molecule inhibitors of the DNA-repair enzyme poly-(ADP-ribose) polymerase (PARP). One of these covers the current clinical development of the lead agent (Jones and Plummer) and the second describes a novel mode of action, so called "synthetic lethally", that may give this agent class specific utility against cancers defective in homologous recombination through, for example, the loss of BRCA2 (Kyle et al). Vascular biology is also the subject of two papers, with one focusing on vascular disrupting agents that affect established vasculature (Tozer et al) and one describing the use of anti-angiogenic agents in combination with radiotherapy (Williams et al). Both detail therapeutics in advanced clinical development. New hope for the treatment of childhood neuroblastoma is presented in the form of a combined treatment strategy using topotecan and the targeted radionuclide [¹³¹I]meta-iodobenzylguanidine (McCluskey et al). The trials and tribulations of the clinical use of epidermal growth factor receptor inhibitors in combination with radiotherapy are also reviewed in this issue (West et al). The tumour micro-environmental condition of hypoxia is a recurring theme throughout a number of the research articles. It is a particular focus of the pre-clinical paper presented by Dr Rachel Cowen, which details the work that was the basis of her being awarded the British Institute of Radiology's Nic McNally prize for Cancer Research in 2005 (Cowen et al). Additional pre-clinical studies are presented that investigate the role of thioredoxin inhibitors as anti-cancer agents (Mukherjee and Martin) and the use of proteomic-based technologies to identify topoisomerase II-associated proteins in a rational approach to identifying therapeutic agents that would synergize with topoisomerase II poisons (Jenkins).

These are exciting and challenging times in anti-cancer drug development. Hopefully, this issue gives a flavour of new opportunities that are arising as a consequence of our ever-expanding knowledge of cancer biology and the technical advances that have supported rational drug design.

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