Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, UK
Email: j.cuzick@qmul.ac.uk
This special issue explores the underdeveloped field of cancer prevention using pharmaceutical agents. Such an approach has been extremely successful for heart disease and stroke prevention where risk factors such as hypertension or high LDL cholesterol have been elevated to the status of ’diseases’ in their own right and not merely risk factors, leading to the widespread use of drugs for preventive treatment. Significant challenges remain if preventive therapy is to take its place alongside screening and treatment in reducing the ever increasing burden of cancer in our world today.
The papers in this special issue explore progress and impediments to using this approach for cancer prevention. The focus in this collection is on current barriers to acceptance of this approach and how they might be overcome, and not so much on the specific agents that have been shown to be effective for cancer prevention. Andrea De Censi and colleagues discuss breast cancer, where the greatest progress has been achieved in terms of identifying efficacious agents, but where implementation has been very limited. Perception of high toxicity is a major issue, both by the profession and the public, and approaches to dealing with this are explored.
The other papers discuss a range of issues related to identifying individuals who are at increased risk of different cancers, and those who would benefit from specific treatment agents. Phillipe Autier discusses the need to develop agents that will prevent aggressive and potentially fatal disease, pointing out that these are the cases we most wish to prevent. A prime example is breast cancer where a range of agents have been shown to prevent oestrogen receptor positive breast cancer either by targeting the oestrogen receptor with blocking agents (so called selective estrogen receptor modifiers or SERMs) or by dramatically reducing oestrogen production via blocking the aromatase pathway (aromatase inhibitors) in postmenopausal women. However none of these agents have any impact on the development of the more aggressive oestrogen receptor negative cancers. This issue is especially relevant for screening where high risk precursors such as atypical hyperplasia and in situ lesions are often detected. Giulia Veronesi and colleagues explore this issue for lung cancer, where screening often identifies small nodules of undetermined significance, and explores the possibilities for using preventive therapy to shrink these nodules and potentially avoid progression and the need for surgery. Fabrizio Bianchi develops this theme further and discusses the potential role of circulating free-micro RNAs (cf-miRNA) and circulating tumour DNA as biomarkers for early lung cancer and response to treatment.
Eva Szabo reviews the NCI programme on early stage trials to evaluate new cancer agents, and discusses the need for validated biomarkers. She focuses on the role of the use of cancer precursor lesions (so called intraepilthelial neoplasia or IEN) for the development of preventive strategies, both as trial endpoints and as intermediate biomarkers for invasive cancer. Somatic changes in these lesions on the pathway to frank invasive cancers may hold keys to the early molecular changes leading to frank invasive cancer.
Mechanisms involved in the long multi-stage process leading over decades to cancer, and agents which may inhibit specific components of this process are also covered. Adriana Albini et al focus on the role of angiogenesis in the development of cancer and introduce the concept of angioprevention. They point to the need for better biomarkers for angiogenesis – in particular the need for blood based biomarkers for vascular endothelial growth factor (VEGF) and their use for monitoring the effectiveness of preventive therapy. Karen Brown and Alessandro Rufini further develop this theme with an emphasis on phytochemicals such as resveratrol, curcumin and other agents developed from dietary sources. They also explore other ‘liquid biopsy’ sources beyond blood such as urine and saliva. The important need for mechanistic models of the effects of preventive therapy both in animals and in humans is emphasized in order to more accurately identify approaches that should be carried forward to the large, expensive and very time consuming randomised trials that will ultimately be required to establish efficacy.
All in all, this special issue provides an excellent focus as to where we are in the field of cancer prevention with therapeutic agents and what needs to be done for this to have a major impact on cancer control. I hope you find it interesting and informative reading.
Acknowledgments
The work included in this special issue was presented at the WP2 Eurocan Platform meeting: European recommendations for biomarker-based chemoprevention trials, October 13-14, 2014, at the European Institute of Oncology, Milan, Italy.
