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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.
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.
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.
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.
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.
Cancer is a widespread deadly disease; annually, one million new breast cancers are diagnosed globally. Endometriosis is a poorly understood disorder, with 80 million patients worldwide. Current therapies for both are inadequate and discovery of new drugs is critical. The Bath group has pioneered identification of new targets and designed two "first-in-class" clinical drugs. The Bath/Imperial College spin-out company Sterix (subsequently acquired by a major pharmaceutical company) has translated them into patients and to the pharmaceutical industry. The steroid sulfatase inhibitors, Irosustat and J995 have entered eighteen clinical trials worldwide in patients with these hormone-dependent diseases, with several ongoing since 2008. Disease was stabilised for cancer patients; the advanced clinical evaluation of both drugs is in progress.
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.
A novel test for prostate cancer was developed from research in mitochondrial genetics conducted at Newcastle University. The Prostate Core Mitomic Test was the first of its kind and is now commercially available in North America. It provides molecular evidence to confirm conventional pathology results showing that men identified as being at risk of prostate cancer are, at the time of examination, free of disease. This is an important patient benefit, as conventional pathology has a 30% chance of missing prostate cancer. The Mitomic test obviates the short-term need for a follow-up biopsy, which is an invasive and very uncomfortable procedure. It is also capable of identifying some men at high risk of having prostate cancer that conventional pathology would miss. The test was introduced to the American market in June 2011 and has generated a multi-million dollar investment and turnover.
Bladder cancer is the fifth most common form of cancer, with over 70% of cases presenting as non-muscle invasive bladder carcinomas (NMIBC). Research in the Institute of Cancer Therapeutics at the University of Bradford led to the evaluation of Apaziquone (EO9) in phase II clinical trials against high risk NMIBC in The Netherlands, and two multi-centre phase III clinical trials involving 106 centres across the USA, Canada and Europe. A total of 1,746 patients with low or high risk NMIBC received EO9 and significant reductions in the rates of recurrence at two years have been reported. Our research has impacted upon the health and welfare of patients with NMIBC.
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.