Cancer Research Technology (CRT) and The Institute of Cancer Research (ICR) have signed a deal with Dutch drug discovery company, ZoBio BV, to discover and develop drugs to block a DNA repair target which may play a role in cancer cell survival.
CRT will manage commercialisation arising from any potential drug compounds discovered through the collaboration and will share a portion of future revenues with ZoBio and the ICR.
The collaboration will combine the ICR’s expertise in drug discovery and target validation – proving a protein’s importance as a therapeutic target – with ZoBio’s patented drug fragment screening technology called TINS, to identify small molecules that bind to and block the DNA repair target.
DNA damage occurs during each cell division. If DNA damage is allowed to accumulate, cells will stop dividing and may eventually die.
Healthy cells use several different routes to identify and repair DNA damage. But cancer cells, which divide rapidly and accumulate more DNA damage, often have faults with a major DNA repair process. They are forced to rely on ‘back-up’ routes.
Potential drugs developed through the new collaboration would block one of the remaining alternative repair routes. This would cause cancer cells to quickly build up DNA damage and die.
It is also expected that these drugs would increase the effectiveness of common chemotherapies, which work by causing more DNA damage than cancer cells can repair.
Healthy cells could tolerate this type of drug as they divide more slowly and retain their main repair machinery which provides effective DNA repair.
Dr Phil L’Huillier, CRT’s director of business development, said: “Cancer Research UK and the ICR have already made strides in breast cancer treatment by blocking two DNA repair routes at once – people missing the DNA repair protein BRCA can be treated with a drug blocking PARP, an enzyme on a different DNA repair pathway.
“This approach is delivering impressive clinical trial results which could lead to better survival.
“We hope that similar drugs identified through the collaboration could also have promising results, ultimately increasing survival from a range of cancers.”
The project started as a collaboration between Professor Alan Ashworth from the Breakthrough Breast Cancer Research Centre at the ICR, who completed initial validation studies, and Professor Paul Workman from the Cancer Research UK Cancer Therapeutics Unit at the ICR, who will lead the drug discovery programme.
Professor Alan Ashworth, chief executive of the ICR, said: “Collaborations such as this – that pairs our cancer expertise with cutting-edge technology – are key to developing new therapeutics which we hope will increase survival from cancer in the future.”
Dr Gregg Siegal, chief scientific officer of ZoBio, said: “We are excited to work with the ICR on such an exciting and novel target. We are convinced that we can provide valuable starting matter through the use of TINS where other approaches have failed.”
Dr L’Huillier, added: “This innovative collaboration brings together skills and knowledge from the world’s top experts in industry and academia to beat cancer.”
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The target validation step in drug discovery tests whether a naturally occurring cellular molecule (the ‘target’) – such as a protein involved in DNA repair – can be switched on or off by a new potential drug ‘candidate’ molecule. Extensive validation tests establish whether blocking or amplifying the activity of this target protein will have the expected therapeutic effect.
Large libraries of molecules – or drug candidates are then screened for their ability to act on the target – called high-throughput screening.
TINS – Target Immobilised Nuclear Magnetic Resonance Screening platform.
TINS is a proprietary technology that combines the robust NMR approach with extreme sensitivity to very weak interactions such as those between a drug fragment and a target.
The principle behind this is known as synthetic lethality, which is a key focus of Professor Ashworth’s research at the ICR.