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A first-in-class anticancer agent discovered in Thurston's laboratory at the University of Portsmouth in the 1990s has been commercially developed and clinically evaluated over the last two decades. SJG-136 was successful in Phase I clinical trials and is completing Phase II clinical trials for the treatment of ovarian cancer and leukaemia, where significant patient benefit is observed. Related molecules based on this parent compound are in drug programmes being undertaken by Seattle Genetics Inc. and Genentech Inc., leading to additional clinical trials. A spin-out company, Spirogen Ltd, was established in 2000 to commercialise the intellectual property generated from the underpinning research, and the company has recently been sold to AstraZeneca for $200m.
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.
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.
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.
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.
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.
Dalgleish proposed a programme to develop thalidomide analogues for their immunomodulatory and anti-neoplastic actions. Working with a small start-up company, Celgene, several analogues including lenalidomide and pomalidomide were developed and entered clinical trials. Both drugs significantly prolong patient survival in myeloma and myelodysplasia and have received FDA and NICE approval for these purposes. Celgene has grown into a large multi-national company with over 5000 employees. Lenalidomide sales were $3.8 billion in 2012.
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.
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.
Before 2010, there was no accepted standard treatment for patients with advanced biliary tract cancer. The ABC02 trial showed that the combination of two drugs (gemcitabine and cisplatin) significantly improves survival, with acceptable side effects. Consequently, national and international guidelines have been revised to recommend this regimen as a standard of care. Furthermore, in ongoing trials of novel therapies, gemcitabine/cisplatin has become the comparator group, and the aim is to improve survival above what this can already achieve.