In 2005, scientists from our Department of Biology became the first to identify prostate cancer stem cells, which are believed to be the ‘root cause’ of prostate cancer.
Since then, supported by a £2.15m award from Yorkshire Cancer Research (YCR), our researchers have been exploring the molecular properties that allow these cells to spread, survive and resist aggressive treatments.
Prostate gland development
Led by Professor Norman Maitland, Director of the YCR Cancer Research Unit based in York’s Department of Biology, our researchers have unearthed new information about how the prostate gland develops.
By studying human prostate tissue, donated by patients in Hull, and supplied as part of a collaboration within Hull York Medical School, the York team identified the underlying mechanism behind the development of the gland.
The researchers, funded by YCR and the EU FP7 Marie Curie ITN PRO-NEST project, see this discovery as an important step towards developing new therapies to treat prostate cancer.
Professor Maitland said: “The prostate gland is lined with specialised cells which make up the epithelium. Diseases that affect this lining are common in the prostate, but until now, very little has been discovered about the mechanisms which regulate prostate tissue.”
Signalling mechanisms
The team of scientists found that there are 80 genes involved in this process, and the main signals responsible for the activation and regulation of this system are retinoic acid - a chemical made from vitamin A which is supplied in our diet - and male sex hormones.
The balance of retinoic acid and male sex hormones involved in the process is highly regulated in a normal prostate gland – this balance is disrupted in prostate cancer.
Professor Maitland said: “The 80 genes and the signalling mechanisms described by the team all provide potential targets for new therapies, which could be used to combat common prostate diseases, including prostate cancer.”
Alongside this pioneering work, the team at York’s YCR Cancer Research Unit has also made another important discovery – new drugs being developed to fight prostate cancer may not be targeting the root cause of the disease.
Genome methylation
The YCR scientists have discovered that a process called ‘genome methylation’, previously thought to drive the development of cancer, probably occurs in cells that are already cancerous. The research found that therapies aimed at reversing this process might not be effective against cancer stem cells: the ‘root’ of the cancer. Just like a weed in the garden, any failure to remove the root allows the cancer to return.
The research reveals a major difference between the cells normally treated in cancer and the underlying ‘stem’ cells.
Dr Davide Pellacani, now at the University of British Columbia in Vancouver, who carried out the study funded by YCR and the Grand Masonic Charity, said: “There are clear implications for the effectiveness of new drugs currently being developed to change the methylation pattern in cancers. At the moment we only treat a proportion of the cells. By breaking the cancer down into its component cell types, we get fresh insights into why cancers come back after treatment. Only by treating all of the cells in a cancer will we approach long term treatment or even a cure.”
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