Cancer Research UK scientists have discovered
mouth cancer can develop along two distinct pathways, an aggressive
or less aggressive route, reveals a study published in the journal
"Cancer Research" today (Tuesday).
The research lays the foundations for further studies that could help
to improve the management of pre-cancerous lesions and possibly prevent
the development of the disease in the future. The researchers from
Cancer Research UK’s Beatson Institute for Cancer Research in
Glasgow took samples from the mouths of 19 people with pre-cancerous
lesions, or spots, 16 patients with mouth cancer and four normal mouths.
They compared these samples, each one made up from thousands of cells,
in an attempt to find out if the disease develops in more than one
way.
The researchers identified two different routes by which mouth cancer
develops, resulting in ‘mortal’ and ‘immortal’ tumour
cells when they are grown in the laboratory. ‘Mortal’ and ‘immortal’ cells
are genetically very different. ‘Mortal’ cells have a limited
lifespan and so will exhaust themselves as they develop into a tumour,
being less likely to spread or recur following treatment. ‘Immortal’ cells
on the other hand are much more resilient and will keep on dividing,
making them more likely to spread and to cause a recurrence - a major
characteristic of aggressive disease.
They found that faults in the p53 gene and missing expression of the
p16 gene were closely associated with ‘immortal’, aggressive
tumours. Importantly, these same changes were also found in pre-cancerous
cells, which grew in laboratory cultures as ‘immortal’ cells.
When it is working normally, the p53 gene stops damaged cells dividing
and should stop cancers growing, which is probably why faults were
found in the p53 gene in ‘immortal’ cells rather than in ‘mortal’ ones.
The p16 gene helps to control the cell regulation process and can prevent
cancer from developing – expression of this was missing from
most of the more aggressive mouth cancer cells.
Lead researcher Professor Paul Harrison, from Cancer Research UK’s
Beatson Institute, said:
“ We found that many of the molecular
changes found in ‘mortal’ and ‘immortal’ cancers
are also found in their respective pre-cancerous lesions, which suggests
that mouth cancer forms in different ways.”
Mouth cancer patients often develop a series of pre-cancerous lesions
over a number of years, due to damaged DNA frequently caused by prolonged
tobacco and alcohol use. Previously scientists thought all mouth cancers
developed via a single route – from pre-cancer to mouth cancer
as the DNA in mouth cancer cells’ progressively accumulated more
damage. This is the first time scientists have established why some
types of pre-cancerous lesions are more likely to develop into more
aggressive cancers. This could be important because using current tests,
it is impossible to predict which pre-cancers will actually develop
into cancer.
Professor Harrison went on to explain:
“ The data we collected
provide strong evidence for the first time that some mouth cancer tumours
are more aggressive than others and are therefore linked to poorer
patient survival. We hope in the future that these findings will allow
us to discover early on who needs urgent treatment and possibly offer
new methods of preventing the disease.”
Professor John Toy, medical director at Cancer Research UK, said:
“ Cases
of mouth cancer in the UK have risen by a quarter over the past 10
years so these are valuable findings that will help scientists gain
a clearer understanding the ways the disease can develop and progress.
_ 1,600 people die every year from
the disease and Cancer Research UK has launched an awareness campaign ‘Open Up to Mouth Cancer’ to
encourage people to spot the early signs of the disease and reduce
their risk. The most common indicators of mouth cancer are sores, ulcers,
red or white patches and unexplained pain in the mouth or ear. Less
common signs include a lump in the neck, a persistent sore throat or
difficulty swallowing. If any of these persists for more than three
weeks they need to be checked out by a doctor or dentist.”
Journal Ref:
Divergent routes to oral cancer. Hunter et al. (2006).
Cancer Research. Vol 66, Issue 15.
This work was supported by Cancer Research UK, the University of Glasgow,
Strathclyde University and a grant from the Engineering and Physical
Sciences Research Council (EPSRC).
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