Friday 27 August 2010
The Institute of Cancer Research (ICR) and Horizon Discovery (Horizon) are forming a collaboration aimed at rapidly screening the human genome for novel drug targets that selectively kill cancer cells.
By combining Horizon’s panel of 200-plus genetically-defined ‘X-MAN’ cancer models (cellular model that harbors cancer-causing genetic mutations along with a matched-normal parental cell) with ICR scientist Professor Alan Ashworth’s world-class expertise in genome-wide functional genomics, the collaborators endeavor to uncover genetic weak-spots in cancer cells enabling their selective targeting by anti-cancer agents.
Professor Ashworth, Director of the Breakthrough Breast Cancer Research Centre at the ICR, has elegantly demonstrated this concept of ‘synthetic lethality’ previously with his discovery that PARP-inhibitors show dramatic selectivity for breast cancers carrying mutant BRCA genes. PARP-inhibitors are now showing great promise in early-stage clinical trials on patients carrying defective BRCA genes.
Horizon’s co-founder Dr Chris Torrance, while in the renowned Vogelstein laboratory at Johns Hopkins University, has also demonstrated the power of using genetically-defined tumour versus normal (isogenic) human cell-line pairs to rapidly perform synthetic lethality screens on specific cancer-causing genetic lesions.
Together, Professor Ashworth and Horizon will build a high-throughput synthetic lethality screening platform based on the latest generation of pooled shRNA libraries and deep-sequencing technologies. By deploying X-MAN isogenic cell-lines in such screens, a focused list of genome targets that represent key nodes of therapeutic intervention in specific cancer patient populations will be identified.
ICR and Horizon also intend to use a comprehensive ‘personalised’ cancer-target hunting capability in collaboration with other companies who wish to rapidly identify new targets and biomarkers that may effectively address specific patient cohorts. This could enable the more rapid and successful translation of oncology drug candidates into clinical use.
Professor Ashworth says: “We are excited by the opportunity offered by this collaboration between the ICR and Horizon of combining two cutting-edge technologies. We are confident that the synergy between these two partners will enable us to move projects from the laboratory bench to the bedside very rapidly.”
Dr Chris Torrance, CEO of Horizon Discovery Ltd, says: “We are proud to be working with Alan’s lab to build a comprehensive picture of synthetically lethal targets, which have proven ability to effectively attack cancer at its causative roots. Moreover, we will use the X-MAN models to more effectively deconstruct the many important cancer genotypes for which conventional pharma drug discovery pipelines have still not yielded viable drug candidates or targets, such as mutant K-Ras and p53. Such genes are major drivers of cancer development and their resistance to existing therapies.”
-ENDS-
Media Contact: ICR Science Press Officer Jane Bunce on 0207 153 5106
Horizon Discovery
Horizon Discovery is a translational genomics and personalised medicine company founded in June 2007 and is headquartered at IQ Cambridge, Cambridge, UK and with additional research laboratories in Torino, Italy. Horizon’s goal is to convert new information on the genetic causes of cancer into laboratory models that will facilitate the discovery of drugs that target these defects. Central to this aim is Horizon Discovery’s offering of X-MAN isogenic cell-lines, which represent accurate models of defined cancer patient populations and their matched normal genetic backgrounds – a missing link in the rational and efficient development of novel targeted anti-cancer agents. These X-MAN models are now being used to speed up and rationalize every phase of the drug development process; from the discovery of cancer targets and biomarkers to the design of more rational clinical trials based around the patients most likely to respond.
The Institute of Cancer Research
- 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
Breakthrough Breast Cancer
- Breakthrough Breast Cancer is a pioneering charity dedicated to the prevention, treatment and ultimate eradication of breast cancer fighting on three fronts: research, campaigning and education.
- Breakthrough Breast Cancer funds ground-breaking research, campaign for better services and treatments and raise awareness of breast cancer. Through this work the charity believes passionately that breast cancer can be beaten and the fear of the disease removed for good.
Find more information at breakthrough.org.uk