The Institute of Cancer Research (ICR) has announced that an experimental drug it helped discover has started Phase I safety testing in patients with a range of cancer types.
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 said: “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.”