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New partnership model needed to explore kinases for cancer treatments


International leaders in drug discovery have warned that a huge reservoir of potential targets for new cancer drugs will remain unexplored unless non-profit research organisations and pharmaceutical companies come together in a new model of large-scale partnership.

A strongly argued commentary in the journal Nature Chemical Biology from a group of international experts calls for a new era of public-private partnership to realise the enormous but largely untapped potential of a group of proteins called kinases as targets for new cancer therapies.

The authors, among them leading researchers at The Institute of Cancer Research, London, hope that a large worldwide consortium of research institutions, charities and pharmaceutical companies could more effectively carry out new kinase research, avoid duplication of effort and share the early risk involved in the discovery of biological targets with the potential to benefit patients with cancer and other diseases.

Despite the widely accepted potential of kinases as drug targets, only nine out of 518 of these have been targeted by new treatments so far. The authors believe this situation must change – and propose that a large-scale international partnership model is the best way to accelerate progress.

This extensive collaborative model would support the financially risky early discovery of quality small molecule chemical probes – small-molecule chemicals and prototype drugs to enable biological studies on the role of kinases in many different diseases.

Professor Julian Blagg, one of the authors of the commentary and deputy head of the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research (ICR), said: “We’re determined to discover and develop new treatments for cancer patients, but we cannot do this alone. It is very difficult and expensive to take something that looks promising in the laboratory and speedily prove that potential in the clinic; to make such an investment of time and effort you also need to be confident the biological target is the right one.”

“Kinases present us with a particular dilemma because they offer huge potential as cancer treatments, but it’s also risky and costly to identity the most exciting potential targets among the many hundreds in the human kinome. It’s a bit like drilling for oil, where both the costs and the potential rewards are huge, and to meet that challenge and share the risk without duplication of effort, we need large-scale public-private partnerships working together in a systematic way.”

The ICR’s non-profit drug discovery team in the Cancer Therapeutics Unit has pioneered a model of public-private partnership in which it resolves much of the early risk to the point where the potential of the target can be demonstrated and commercial partners are willing to co-invest. After that, the ICR works with biotech and pharmaceutical companies to complete pre-clinical research and clinical evaluation. However, due to the large number of potential drug targets among the kinase family of proteins that need to be better understood, the authors propose that the most effective way to exploit the full potential is to join forces with several research institutes and pharmaceutical companies at a very early stage of the drug discovery endeavour – to discover the quality chemical probes that can be used to understand the biology and build confidence in the targets most likely to bring patient benefit. They believe that this public-private partnership approach would be the best and fastest way to obtain broader and deeper understanding of the most promising kinases and avoid unnecessary duplication of research.

Professor Paul Workman, deputy chief executive of The Institute of Cancer Research and head of the Cancer Research UK Cancer Therapeutics Unit at the ICR, said: “Our non-profit cancer drug discovery team at ICR has pioneered a model of public-private partnership in which we take the early risk to the point of proof of concept in laboratory models, after which we partner with industry to work together to complete the late stage preclinical research followed by clinical evaluation. This has worked very well as a solution to the innovation gap between early-stage research and commercialisation and patient benefit. But there are a very large number of potential drug targets in the kinase family of proteins with untapped potential that we urgently need to understand much better – and the most effective way to do this is to join forces with many others to take a broad,  systematic approach. A large-scale public-private partnership would be an innovative new way forward that could allow us much more rapidly to develop a broader and deeper understanding while reducing duplication. The early stage benefits will be chemical tools to improve our understanding of biology – but the most important outcome would be a whole range of innovative new drugs for patients with cancer and other life-threatening diseases.”

The ICR’s work in undertaking smaller scale, one-off public-private partnerships has a significant track record of success. The Cancer Therapeutics Unit at the ICR and the Drug Development Unit at the ICR and The Royal Marsden won the 2012 AACR Team Science Award in recognition of their discovery, with academic and commercial collaborators, of 16 preclinical development candidates for the treatment of cancer since 2005, of which six are currently in clinical trials. Professor Workman also won the Royal Society of Chemistry 2012 Chemistry World Entrepreneur of the Year award for his role in establishing and nurturing biotech investment in oncology research and drug discovery.

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