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A new way to design cancer drugs

  • Researcher: Dr Daniel Lietha
  • Institution: Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • Award Amount: £161,645 for 3 years from 1st June 1016
  • Cancer Type: General Cancer Research
A new way to design cancer drugs
In this project Dr Daniel Lietha and his team aim to discover a new type of cancer drug that acts on a molecule called Focal Adhesion Kinase (FAK).  FAK is an important signalling protein that passes on messages from growth factors and other molecules in the environment surrounding the cell to orchestrate important cellular processes, such as cell growth, movement and survival. In cancer cells, FAK is frequently present at too high levels meaning the cells grow too rapidly, forming a tumour.  There is evidence that blocking FAK can be a successful strategy to treat a number of solid tumours.  However, most current FAK drugs lack high specificity, meaning they also affect other helpful molecules and are therefore quite toxic. Dr Lietha wants to find alternative types of FAK inhibitors, so-called allosteric inhibitors, which are usually highly specific.  He explains “The places where the allosteric drugs stick to the target are usually shallow molecular surface pockets that are difficult to target. Ideally there would be a deep crevice in the molecule where we could wedge in a drug and block its function.  Since we target small and shallow surface pockets,we aim to use smaller-than-drug-like chemical compounds for initial screening find initial small-molecules that stick weakly to such allosteric sites. We will analyse exactly how the molecules stick and use this information to design more elaborate and drug-like compounds that stick more tightly to the target molecule; in our case FAK” He added “Targeting allosteric sites is challenging but we hope to discover some highly selective chemical compounds that block FAK and provide starting points towards new drugs to treat cancer.” He concluded “For me this project is exciting because for the first time we can use very basic insights we obtained in the lab on how FAK is regulated naturally in the cell to design chemicals that can interfere with this native regulation and thereby block FAK function in a highly specific manner.”
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