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Newcastle University research discovered the first potent inhibitors of the DNA repair enzyme poly (ADP-ribose) polymerase 1 (PARP-1) through medicinal chemistry and preclinical work leading to first-in-man clinical studies. This research led to the development of Rucaparib, an agent that inhibits the ability of cancer cells to survive drug treatments or radiotherapy. As a result of Newcastle's research a further 8 PARP inhibitors are in development. Major pharmaceutical companies have invested an estimated $385 million in clinical trials, with at least 7000 patients enrolled in PARP inhibitor trials since 2008. Cancer patients worldwide have already been successfully treated with these new anti-cancer drugs.
Laboratory research at Imperial College supported the concept of switching adjuvant treatment of breast cancer (i.e. tamoxifen for 2-3 years to exemestane for 2-3 years) which has now been shown in Imperial-led clinical trials to improve overall survival of breast cancer patients for at least 5 years post-switching. In association with this, the effects of switching on endometrial, skeletal and joint function have shown few long-term deleterious effects. This way of treating breast cancer has now gained acceptance worldwide, as being more efficacious and resulting in fewer longterm, serious side effects. It is the recommended treatment in international guidelines.
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.
Bowel cancer is the third most frequently diagnosed cancer worldwide. University of Glasgow researchers have established Xeloda (an oral 5-fluorouracil precursor) and XELOX (a chemotherapeutic regimen combining Xeloda with oxaliplatin) as highly effective, targeted therapies for patients with bowel cancer. Since 2008, European regulatory approval of these therapies has been incorporated into major international clinical guidelines. The research has transformed patient care by improving the treatment experience, with more convenient dosing schedules and fewer side effects compared with previous chemotherapy procedures. Xeloda and XELOX have transformed chemotherapy for bowel cancer and decreased therapeutic costs, potentially saving around £4,762 (Xeloda) and £947 (XELOX) per patient for the NHS.
University of Glasgow research has led to the adoption of first-line chemotherapy for ovarian cancer, which has improved patient survival by 11% and has been used to treat 66% of women with ovarian cancer since January 2011 in the West of Scotland Cancer Care Network alone. These therapies are recommended by guidelines for ovarian cancer treatment in the USA, Europe and the UK. The USA guidelines are disseminated to 4.3 million people worldwide and the European guidelines reach 15,000 health professionals. The UK guidelines are used to identify those drugs that are funded by the NHS and used in NHS hospitals.
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.
Work by Professor Andrew Tutt at King's College London (KCL), has had the following major impacts: (i) it has provided proof through first-in-man clinical trials (in collaboration with the Royal Marsden/ICR Phase I Clinical Trials Unit) and Phase II clinical trials designed and led by Professor Tutt that poly(ADP ribose) polymerase (PARP) inhibitors have an anti-cancer action in breast and ovarian cancers with BRCA mutations; (ii) it has demonstrated that the concept of `synthetic lethality' can be applied to the selective targeting of cancer cells in humans; (iii) it has paved the way for a major programme of investment by the pharmaceutical industry (over $1 billion to date) in PARP inhibitors for the treatment of BRCA-related cancers (which are currently being tested in a range of cancers in Phase III trials); and (iv) it has been incorporated into UK, European, US and other international guidelines on genetic testing for breast and ovarian cancers that run in families.
The Cancer Research UK Formulation Unit at the University of Strathclyde performed the pharmaceutical research and development of new chemotherapy treatments for malignant brain and prostate cancer (temozolomide and abiraterone acetate). These two drugs are now marketed globally, with FDA approval for the US market in 1999 and 2011 respectively, and have directly improved the quality of life and increased survival rates during treatment for over a quarter of a million cancer patients annually since 2008. Temozolomide achieved $1 billion sales per annum in 2008, and Abiraterone global sales reached $1.45 billion by 2013. Both drugs have produced economic benefit to the charity Cancer Research UK through royalty payments.
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.
As part of a 20 year partnership with AstraZeneca, Professor John Robertson, University of Nottingham, has made the largest and most consistent contribution by a clinical academic to the development of the most recent endocrine agent licensed for breast cancer, fulvestrant (Faslodex®). [text removed for publication]. Since 2008, fulvestrant 250mg has continued to be registered and launched in a number of countries based on Robertson's work, and Robertson has enhanced the clinical uptake of fulvestrant 250mg through training. His research has also been instrumental in the development and uptake of the more efficacious fulvestrant 500mg, including registration in 2010.