The high-profile Genesis conference is held in London each December to showcase the best of the UK’s research in biotechnology and provide opportunities for industrial and academic scientists working in the field to build new contacts. The ninth Genesis took place in the Queen Elizabeth II conference centre in Westminster on December 10 and 11, 2009. As always, it was organised by London First and the London Biotechnology Network, and LBN’s director, Tony Jones, must take credit for assembling an excellent programme in undoubtedly challenging economic circumstances. The importance of cancer as a research area, and the innovative nature of research in the field, was highlighted by the choice of Karol Sikora of Cancer Partners UK and Kathy Oliver of the International Brain Tumour Alliance as the first two speakers in the opening plenary session.
Karol Sikora is a distinguished oncologist and author of many books, including Treatment of Cancer (1990), which is still the standard postgraduate oncology textbook in the UK. He is medical director of Cancer Partners UK, a new independent organisation set up by experts to improve the quality of and access to cancer services throughout the country. His presentation focused on the difficulties of funding access to the most innovative, targeted cancer therapies, and on ways of overcoming these.
Whereas, as late as the mid-twentieth century, cancer patients were kept largely in ignorance of their condition, they now have full access via the Internet to information about the disease and its treatment, and, just as importantly, about treatments they are not entitled to. The EGFR inhibitor erlotinib, marketed as Tarceva, (http://www.tarceva.com) is a case in point. NICE controversially rejected this drug for pancreatic cancer, yet it has been made fully available in France. Yet it may be appropriate to ask which of these decisions is correct, since its licence for this indication was based on a mean increase in life expectancy of just eight days. And even with NICE as a gatekeeper, BUPA has estimated that the cost of cancer drugs have increased by 250% since 2000 and will continue to rise dramatically.
The implication that innovation in cancer therapeutics, by developing drugs that few can afford, provides as many challenges as opportunities is difficult to avoid. Sikora explained that many of these could be overcome by more sophisticated diagnostics. If cancer therapies are to be cost effective they must be targeted at those patients with tumours with an appropriate molecular signature. It is just as important to develop tests for the genetic and epigenetic changes that define a particular tumour as to design drugs to target it. But there is an economic problem here too. Diagnostics development is costly, yet its rewards are relatively small. A successful diagnostic test is worth millions as compared to billions for a blockbuster drug. We may need to re-think the ways in which diagnostics development can be funded if tests are to reach the clinic and patients to benefit from the most appropriate treatment from an increasingly extensive – but expensive – range.
The patients' perspective was provided by the next speaker, Kathy Oliver, Co-Director of the International Brain Tumour Alliance (www.theibta.org). Oliver, formerly a journalist, described how her life was changed five years ago when her son was diagnosed with a brain tumour. "We felt like travellers in a strange and surreal world. We didn't speak the language. We didn't know how to get from A to B. We had no map, no compass, no anchor to steady us." she explained. Since then, she has become active in the international brain tumour community, advocating for better care and support for patients with this disease, and for their carers. Oliver spoke eloquently about inequalities in access to promising therapies; a shortage of funding for research; and a lack of awareness of and support for the specific challenges of rare cancers like brain tumours. "Even in the richest and most powerful countries on the planet," she said, "patients can be lost in a maze of uneven and inequitable care."
The afternoon showcase of UK drug discovery technology was divided into three sessions; imaging in drug development, preclinical strategies, and “next wave” technologies. In each session, there were speakers who stressed applications of their companies’ technologies to cancer. In the imaging session, Jonah Aburrow-Jones, standing in for Harry Hatzakis, CEO of imaging company Biotronics3D, spoke about advances in tumour imaging. Imaging has developed in recent decades from two to three or even (with video and time-lapse imaging) four dimensions. Several modalities, including CT, MRI, PET and ultrasound are in regular use for both diagnosis and clinical cancer research, with research requiring higher standards of accuracy and prevision than relatively routine diagnosis. Aburrow-Jones spent much of his presentation discussing the possibilities offered by distributed computing. It is now possible to analyse imaging data remotely over the Internet, which can be a great boon for clinicians in poor and remote communities, and Web 2.0 tools are being used to set up collaborative networks of clinicians and researchers involved in image analysis.
The Preclinical Strategies session featured two talks with more indirect application to oncology. Jane Dancer, vice-president for business development at CellZome, a company that spun out of the European Molecular Biology Laboratory in 2000, described a novel proteomics based method to discover and develop specific kinase inhibitors. The Kinobeads technology involves isolating a number of ATP mimetics bound to a “bead” and exposing this to a sample of tissue. Kinases and other purine-binding proteins will bind to these; bound proteins are isolated, their inhibition profile characterised using techniques such as quantitative mass spectrometry, and molecules with the required kinase-binding profile identified. Scientists at CellZome are using this technique to design novel kinase inhibitors for inflammatory disorders and, interestingly, Parkinson’s disease. However, the technique is equally applicable to oncology: all the eight kinase inhibitors currently licensed for use in the clinic are anti-cancer drugs. David Cook, Associate Director for Global Safety Assessment at AstraZeneca, discussed novel tools for predictive toxicity that aim to predict likely toxicities early in the drug discovery pathway, if possible in silico, and to build them in to quantitative structure-activity relationships in order to eliminate compounds with expected toxicity as early as possible.
In the final session, on “next wave” technologies, Steven Zimmer of e-therapeutics gave an intriguing presentation introducing and explaining the paradigm of systems biology and how it applies to drug development. Systems biology, he said, could be defined very simply as “physiology with numbers”. It is a way of looking at diseases and drug interventions within networks, organs and systems rather than pathways or single targets. Biological networks often have built-in redundancy, so when a signal transduction protein such as a kinase is inhibited, for example, another protein will “step into the breach”: normally a protection against system failure, but sometimes a source of drug resistance. One case study discussed was the development of a model interaction network for melanoma; this has already been used to identify a candidate drug for this indication in a molecule that had previously failed clinical trials as a neuroprotectant.
Genesis 2010 will be a one-day event at the same location, and will be held on December 9 next year. It is likely that there will be plenty to interest the cancer community there too.