Molecular chaperones play an essential ‘escort role’ by ensuring that newly made proteins adopt the correct shape to function correctly and help normal cells to respond to stress. However, new research has suggested that these same chaperones also contribute substantially to the activity of cancer-causing proteins and actually help cancer cells to survive and become more aggressive.
Professor Paul Workman, director of the Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research (ICR)'s Sutton site, said: ’We are very pleased to work with AstraZeneca, who bring great expertise in cancer drug discovery and development. By working together in this collaboration, we hope to exploit an ”Achilles heel” in the chaperone and stress pathways of cancer cells that will lead to the discovery of new powerful drugs to fight cancer.’
As part of the deal, AstraZeneca will contribute more than £4 million to the three-year project. The ICR will lead the scientific work, utilizing £1.6 million in funding from Cancer Research UK, who supported the original laboratory-based discovery on which this work will now build.
Researchers at the ICR have revealed many details of how molecular chaperones assist with the production of cancer-causing proteins and how they help cancer cells to survive in the stressful tumour environment. In addition, the work has shown how cancer cells become much more dependent than healthy cells on molecular chaperones for their growth and survival, which makes molecular chaperones excellent targets for cancer treatment. The ICR team has already shown how several of the components of the chaperone system can be targeted to block the growth of cancer cells. This collaboration will look for new proteins, excluding the well-established HSP90 protein, to target in chaperone pathways. The hope is that this research will enable scientists to find new ways to intervene in chaperone functions. Novel drugs that act in this way could result in the more effective destruction of cancer-causing proteins and at the same time antagonize the protective survival functions of chaperones, leading to powerful and selective killing of cancer cells. Full details of these novel targets have not been published, but the ICR scientists have published extensively on the components of the stress pathway and on related chaperone targets.