This novel drug blocks an enzyme that is involved both in cancer development and in tumours becoming resistant to a number of important existing anti-cancer drugs. Inhibitors of Protein Kinase B (PKB, also known as AKT) have the potential to treat a broad range of cancer types, including breast, prostate, ovarian, pancreatic and gastric cancers.
A Phase I safety trial for the drug, known as AZD5363, has started recruiting at The Royal Marsden NHS Foundation Trust and the Christie Hospital NHS Trust in the UK, and in the Netherlands, funded by AstraZeneca.
The ICR has a long interest in the potential of PKB as a cancer drug target, beginning when the ICR’s Professor David Barford became the first in the world to determine the enzyme’s crystal structure. This detailed 3D understanding of PKB opened the door to developing a chemical compound that could lock on to PKB and block its function.
A collaborative drug discovery programme began in 2003 between the ICR, the UK-based biotechnology company Astex Therapeutics and Cancer Research Technology Limited (CRT). Led at the ICR by Dr Michelle Garrett of the Cancer Research UK Cancer Therapeutics Unit, with Dr Ian Collins as lead chemist, the collaboration identified a number of promising inhibitors. Following further collaboration with Astex, the pharmaceutical company AstraZeneca announced in January 2010 that it had selected the specific compound AZD5363 to progress to the clinical trial stage.
The Phase I study is now recruiting patients with advanced solid tumours and aims to determine the safety, tolerability and preliminary anti-cancer activity of AZD5363. It will also identify a treatment dose that can be used in later stage trials.
Professor Paul Workman, Director of the Cancer Research UK Cancer Therapeutics Unit at the ICR, said: “After many years of research into the enzyme PKB, we are delighted that this inhibitor has reached the patient trial stage. This inhibitor is one of a number of new-generation drugs designed to target the genetic defects responsible for causing various cancers, and which have the potential to be used as part of personalized treatments that have greater activity and fewer side-effects than traditional drugs.”
Dr Udai Banerji from the ICR and The Royal Marsden Hospital will lead the UK arm of the clinical trial. Dr Garrett and her team will conduct a related investigation, assessing whether it is possible to predict the drug’s effectiveness in patients by testing their blood and tissues for specific biological indicators (biomarkers) including phospho-PRAS40 and circulating tumour cells.
Dr Banerji says: “We believe that PKB inhibitors could potentially halt the growth of a wide range of cancers, including some that presently have very few treatment options. We are very pleased that patients could soon benefit from this exciting new approach.”
Media Contact: Science Communications Manager Jane Bunce on 0207 153 5106 or after hours 077217 47900
Notes to editors:
PKB is a key enzyme in the PI3K/PKB/mTOR tumour cell survival pathway.
For more information on the trial visit http://clinicaltrials.gov/show/NCT01226316
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.
- The ICR is home to the world’s leading academic cancer drug development team. Several important anti-cancer drugs used worldwide were synthesised at the ICR and it has discovered an average of two preclinical candidates each year over the past five years.
For more information visit www.icr.ac.uk
The Royal Marsden Hospital
The Royal Marsden was the first hospital in the world dedicated to cancer diagnosis, treatment and research into the causes of cancer. Today, as The Royal Marsden NHS Foundation Trust, together with its academic partner The Institute of Cancer Research, form the largest comprehensive cancer centre in Europe with over 40,000 patients from the UK and abroad seen each year. It is a centre of excellence, and was the only NHS Trust to achieve the highest possible ranking in the Healthcare Commission’s Annual Health Check for four year in a row. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.
For further information please contact Naomi Owen on 0207 808 2107