Australian research achievement identifies less aggressive cancer cell

In just eight years, a fundamental discovery made by an Australian team of scientists looks like moving from concept to clinic.  In the world of medical science, this is exceptionally rapid progress.

The first step in this story was their discovery in 1995 of another way cancer cells can escape from the normal limits on cell proliferation.  Named ALT (for Alternative Lengthening of Telomeres), this is a mechanism used by some cancers to overcome the progressive erosion of telomeres (chromosome ends) that occurs when normal cells proliferate.  The team has subsequently made a number of discoveries about ALT, including the presence of a novel structure inside the nuclei of ALT cells.  Their recent findings about the nature of the ALT mechanism received international acclaim, and raised the prospect of eventually finding novel anti-cancer treatments that target this key aspect of cancer cells.

The news today is that the current issue of  The Lancet describes a study showing that ALT is often present in a common and lethal type of brain tumour (called glioblastoma multiforme), and appears to have a major influence on the aggressiveness or otherwise of this cancer.  In other words, the presence or absence of ALT makes a substantial difference to patient outcome and survival.  The researchers found that most of the long-term survivors have ALT, suggesting that AT tumours are biologically less aggressive.

The Australian team that discovered ALT is the Cancer Research Unit at the Children’s Medical Research Institute (CMRI) in Sydney, headed by Dr Roger Reddel.  The work has received major long-term support from The Cancer Council NSW and CMRI’s Jeans for Genes campaign.  Since the original discoveries, the team has networked with a number of research groups internationally, including the Sheffield, U.K. researchers who carried out the study revealed in the Lancet article.

“It’s very rewarding to have a basic research discovery translated so quickly into the cancer clinic,” said Dr Reddel.

“The presence or absence of ALT in these brain tumours appears to be the most accurate predictor of outcome yet found”, said Dr Janice Royds, who led the Sheffield group.  If the results are confirmed in further studies, a test for ALT may become routine for prognostic purposes.  A major study is now commencing in New Zealand to test this further.  The CMRI scientists are also building on their discovery of a unique subnuclear structure in ALT cells to develop a test for ALT that can be used in routine histopathology laboratories.