Scientists at The Institute of Cancer Research have discovered an exciting new target in the fight to stop the spread of cancer cells which could significantly improve treatment by replacing traditional chemotherapy.
Deregulated proteins are the driving force behind the uncontrolled growth of cancer cells. Institute structural biologists, funded by The Wellcome Trust, have now shown how these proteins are able to survive, in spite of being damaged.
The key lies in the discovery of the atomic structure of the protein Cdc37. One end of Cdc37 binds the proteins which control cell growth but which can become deregulated and cause cancer while the other end binds a molecule called Hsp90 which helps these proteins fold into the correct, active structure.
By attaching themselves to Cdc37, the deregulated proteins are rescued by Hsp90 which is known as a molecular chaperone, even though these proteins may now be having a destructive effect within the cell.
So Cdc37 rescues the cancer-driving protein by acting as a carrier, allowing it to continue on its destructive path. This discovery has presented scientists working in cancer therapeutics with the challenge of developing new drugs to block this process and prevent the rescue of the deregulated protein.
This could help transform the way cancer patients are treated and replace traditional chemotherapy, since cancer cells would be targeted directly, avoiding any damage to other healthy cells within the body.
The scientists’ detailed structural description will allow The Institute’s experts in cancer therapeutics to design new and highly specific drugs that will stop Cdc37 from binding to Hsp90, thereby depriving the uncontrolled proteins of the help they need to drive cancer.
Professor Laurence Pearl, Chairman of the Section of Structural Biology at The Institute of Cancer Research explains:
“Although this is very basic science, understanding the molecular structure and function of the proteins that drive cancer is crucial to the development of the new generation of drugs that actually target what goes wrong in a cancer cell, so that this kind of research feeds directly into patient treatments.
The Hsp90 system is a particularly attractive target as the cancer-driving proteins in many different types of cancer depend on this chaperone, so one drug may be of value in treating many different forms of the disease.“
Recent discoveries in this area have led to a new multidisciplinary approach to cancer research, meaning that developments can get from the bench to the bedside in the minimum time.
With anti-chaperone drugs such as 17AAG already in trial, it is expected that this new finding will speed up the process of drug discovery, with trials on others expected to begin by the end of 2004.
Professor Paul Workman, Director of Cancer Therapeutics at The Institute of Cancer Research comments:
“This new finding is extremely valuable in helping us understand the role of chaperones and has given us a target for the development of drugs that we hope will revolutionise cancer treatment. The drugs will target the cause of the cancer meaning patients will suffer far less from unpleasant side effects. They have the potential for treating all types of cancer and offer hope to patients with cancers for which there is currently no effective treatment.”
The Institute of Cancer Research is now involved in a 4-way collaboration with colleagues at The Royal Marsden Hospital, Cancer Research UK and commercial partner Vernalis in order to carry forward a programme of drug development to target the chaperone.
Professor Peter Rigby, Chief Executive of The Institute of Cancer Research comments:
“We are delighted that our investment in a multidisciplinary approach to cancer research is bearing fruit. These latest findings have given us a clear way forward for the development of more effective treatments for all forms of cancer which will target the cause of each disease and have fewer side effects for the patient.”