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Research by Professor Steve Jackson led to the discovery of synthetic lethality as a means of selectively targeting cancer cells, and to Jackson founding KuDOS Pharmaceuticals to translate this research into therapies. This novel approach has changed the way pharmaceutical companies develop cancer therapeutics and has led to several drugs reaching pre-clinical and clinical development. The most advanced of these (olaparib, a PARP inhibitor originally developed at KuDOS and acquired by Astra Zeneca) is now entering Phase 3 trials and registration in Europe. In 2011, Jackson founded MISSION Therapeutics Ltd, to extend the synthetic lethality concept into targeting deubiquitylating enzymes to selectively kill tumour cells.
ProtecT (Neal, Cambridge; Donovan, Bristol; Hamdy, Oxford), funded by NIHR in 1999, is the largest randomised controlled trial in localised prostate cancer; and compares a deferred conservative approach (Active Monitoring — developed by the Trial PIs) with surgery and radiotherapy. Avoiding "over-treatment" in low risk cancer is important and Active Monitoring (AM) and Surveillance (AS) have now had a major impact on patients and on national health policy through NICE guidance, which recommends such management approaches. The linked bio-repository was critical to characterising the genetic pre-disposition alleles (SNPs) in prostate cancer, which are now being used to identify high risk populations.
Research carried out at King's College London (KCL) has raised awareness of the potential risks associated with certain hormone therapies used to treat prostate cancer. The group found that such hormone therapy can raise the risk of heart attack by 24% and the risk of dying from heart disease by 21%. However, for men receiving anti-androgen hormone therapy, the risk of dying from heart disease was lower compared to other hormone therapies such as gonadotropin-releasing hormone agonists. With anti-androgen hormone therapy there was a chance of heart failure but the risk was 5% compared to 34% for other hormone therapies which reduce testosterone production.
The research has had very considerable impact in terms of reach, as over 600 articles have been published in newspapers and other media which refer to the KCL finding that men with prostate cancer treated with certain hormone therapies have a higher risk of heart disease and strokes.
The findings had a very significant impact on US Food and Drug Administration (FDA) advice to healthcare professionals on the benefits and risks of hormone therapy. The FDA also required manufacturers of certain hormone therapy drugs to add safety information to labels.
Newcastle research selected the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) as a promising target for cancer therapy. The first-in-class PARP inhibitor, rucaparib, was developed at Newcastle, in collaboration with Cancer Research UK and Agouron Pharmaceuticals, and subsequently became the first PARP inhibitor to be used to treat a cancer patient in a clinical trial. Currently, at least 8 PARP inhibitors are being developed and major pharmaceutical companies have to date invested around $385 million in clinical trials, and over 7,000 patients worldwide have been treated with PARP inhibitors in trials since 2008, demonstrating the importance of basic and translational research in universities to drug discovery by pharmaceutical companies.
Research at Queen's University Belfast has led to the successful development and commercialization of a DNA chip technology platform that facilitates the rapid discovery and validation of new diagnostic tests in cancer. A spin out company has been established called Almac Diagnostics that currently employs 85 staff, thereby significantly contributing to the knowledge based economy in Northern Ireland. Almac has used this technology to develop and validate a number of genomic tests that have been successfully licensed to established US based diagnostic companies, thereby securing long term revenue streams. Almac is now recognised internationally as a worldwide industry leader in this area.
Thousands of people across the world with a genetic predisposition (HNPCC) to bowel cancer, together with the population at large, have benefited from research on aspirin and dietary fibre undertaken at the University of Bristol since 1993. Clinical trials involving the Bristol group show that the incidence of bowel cancer has fallen in HNPCC patients who take aspirin. Moreover, aspirin use after diagnosis of bowel cancer has reduced colorectal cancer mortality. Furthermore, a high fibre diet also lowers the risk of bowel cancer. These studies led to national public health initiatives (such as the `five-a-day' campaign) that have been instrumental in increasing public awareness of the importance of aspirin and dietary fibre in reducing the risk of bowel cancer, and in establishing international guidelines on dietary advice.
Researchers at the University of Sheffield developed a novel tailored therapy for some forms of breast cancer. This was the first example of the selective killing of a tumour using an inhibitor of a DNA repair enzyme (PARP) to induce synthetic lethality, heralding an era of personalised cancer therapy. The discovery was patent protected and development rights sold to Astra-Zeneca who undertook successful phase I and II clinical trials. Disclosure of the findings stimulated intense investment in research and development and has revolutionised approaches to cancer therapy. There are now eight PARP inhibitors in phase I to III clinical trials (92 currently listed involving several leading pharmaceutical companies and thousands of patients) targeting a wide range of tumour types.
The University of Nottingham spin out company Scancell Holdings plc is developing novel immunotherapies for the treatment of cancer. By licensing products (£6million) and listing and raising money (£4million) on the stock exchange, it has provided an excellent return for investors. In 2012, in response to good clinical trial results, Scancell's shares showed the greatest percentage increase (10fold) on London's AIM stock exchange, reaching a market capitalisation of £98million. This has encouraged further investment (£6.5million) which is in line with the Government's plan to promote the Biotechnology Industry. As the products progress to market it will save further lives and continue to increase in value providing further profit for investors.
Improvements in therapy have increased the 5-year survival rate for a number of cancers, leading to a new focus on promoting the health and wellbeing of cancer survivors. In the UK alone, over 500,000 people have physical or psychological consequences associated with cancer or its treatment.
Research at the University of Surrey has led to the development of self-management interventions for cancer survivors, demonstrating that active patient involvement leads to significant health and wellbeing benefits. These studies have driven national and international practice policy in the management of the consequences of cancer and its treatment.
Research within the Northern Ireland Barrett's oesophagus Register demonstrated that cancer risk in this disease was substantially lower than previously thought. It identified clinico-pathological characteristics and potential biomarkers that allow Barrett's patients to be stratified into those with higher and lower cancer risk. This research has influenced recommendations from Gastroenterological Associations in the UK and USA and resulted in altered clinical practice nationally and internationally, in which costly routine endoscopic surveillance is now targeted to Barrett's oesophagus patients with the highest cancer risk.