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 Ashworth, Chief Executive of the ICR, says: "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 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.”
March 29 2012 - Read article ›
*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.
About The Institute of Cancer Research (ICR)
• The ICR is Europe’s leading cancer research centre
• The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise
• The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe
• The ICR has charitable status and relies on voluntary income, spending 90 pence in every pound of total income directly on research
• As a college of the University of London, the ICR also provides postgraduate higher education of international distinction
• Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world
For more information visit www.icr.ac.uk
ZoBio BV
Starting with its core TINS (Target Immobilized NMR Screening) fragment screening technology, ZoBio provides an array of biophysics services to support fragment-based drug discovery. These services form an integrated pipeline that includes fragment discovery, validation/characterisation by orthogonal methods such as SPR and NMR-based structural biology services. TINS has been used to discovery highly diverse, efficient ligands for a variety of targets including kinases, protein-protein interaction targets, anti-virals and membrane proteins.
For more information visit www.zobio.com.
Cancer Research Technology (CRT) is a specialist commercialisation and development company, which aims to develop new discoveries in cancer research for the benefit of cancer patients. CRT works closely with leading international cancer scientists and their institutes to protect intellectual property arising from their research and to establish links with commercial partners. CRT facilitates the discovery, development and marketing of new cancer therapeutics, vaccines, diagnostics and enabling technologies. CRT is a wholly owned subsidiary of Cancer Research UK, the world's leading cancer charity dedicated to saving lives through research. Further information about CRT can be found at www.cancertechnology.com
CRT's discovery laboratories build on exploratory research to create attractive commercial opportunities through collaboration with research institutes worldwide. Therapeutic programmes are then out-licensed for further development following identification of a suitable partner.
© Cancer Research Technology 2012