This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
About 500 proteins involved in several types of cancer have already been identified; however, existing drugs can only act against 5% of them. A major part of research is therefore geared towards finding compounds that act against orphan proteins, whose active ingredients must, consequently, be innovative. This is key, say researchers, to design therapies that adapt to each patient’s type of cancer: the quest for personalised medicine, that is more effective and causes fewer side effects. A peculiar family of proteins that could become the target of a new generation of cancer drugs, some of which are already undergoing clinical trials, are molecular chaperones. Some of the leading international experts in this field will be discussing their latest developments next week at the Spanish National Cancer Research Centre (CNIO) in Madrid.
The CNIO-“la Caixa” Foundation Frontiers Meeting ‘Molecular Chaperones in Cancer’, will be held from 2 to 4 May. The meeting, which brings together researchers from Europe, the United States, Japan, and Australia, has been organised by Nabil Djouder (CNIO); Wilhelm Krek (ETH Zurich); Paul Workman (The Institute for Cancer Research, London); and Xiaohong Helena Yang (Cancer Cell, Cambridge, USA).
THE MOLECULAR ‘911’ FOR CELLS
Molecular chaperones belong to a family of evolutionary highly preserved proteins known as heat shock proteins (HSP). They exist in all types of organisms, including bacteria, indicating that they are tremendously important, and are, in metaphorical terms, the cell’s 911 service: the response to any cellular emergency.
Heat shock proteins make it possible for cells to survive under conditions of stress. They were discovered in the 1960s when a researcher heated fruit flies (Drosophila melanogaster, a regular model organism used in laboratories) and noticed that, within a few minutes, these animals synthesised large amounts of what we now call heat shock proteins. We now know that the cold, UV radiation, changes in pressure, and other types of damage also enable stressed cells to produce these proteins.
As explained by Paul Workman, president of The Institute of Cancer Research (ICR) – one of the main cancer drug research centres in the world – cancer cells present specific types of damage due to their very nature, and chaperone proteins are precisely what enable them to survive that damage. In other words, a tumour cell needs chaperone proteins to survive and proliferate. Therefore, a possible strategy to combat cancer would be to block the chaperone proteins.
A NEW GENERATION OF DRUGS THAT COMBAT CHAPERONE PROTEINS?
Workman has been one of the main proponents of this strategy for more than a decade; in particular regarding the molecular chaperone HSP90. In its day, it was a controversial idea, said Workman, because molecular chaperones are also essential for healthy cells. But today, 16 compounds that block the action of HSP90 are being explored, and Workman is hopeful, especially in relation to their use to combat breast cancer. Their role could eventually also be important to combat the emergence of resistance to new personalised medicine treatments.
Workman, under whose leadership the ICR has tested a score of new cancer drugs, has coined the expression Drugging the cancer genome to highlight the need to “discover innovative drugs that act on orphan proteins, instead of developing ‘me too’ type drugs, which simply mimic the effect of already known drugs”, he says.
The results of these trials involving HSP90 and other molecular chaperones will be presented at the next CNIO-“la Caixa” Foundation Frontiers Meeting. More basic issues will also be addressed, such as our understanding of exactly how chaperone proteins carry out their functions in cells and what their role in cancer and other ageing processes are. The latter will be the topic of the opening speech at the conference by Richard Morimoto, from Northwestern University in Evanston, USA.
“Chaperone proteins play an essential role in protein folding, stability, and activity in healthy and pathological cells, including cancer cells”, explains Djouder. “However, despite recent progress, we still have much to learn about the precise details of how they work and how they promote cancer proliferation, often creating interactive networks”.
One of the researchers who will focus on the role of chaperones in the correct folding of cellular proteins is Johannes Buchner, from the Technical University of Munich, Germany.
The meeting is being held in memory of the researcher, Susan Lindquist, from the Massachusetts Institute of Technology (MIT), who died of cancer in 2016.