New test finds chink in cancer's armour

By Tim Dean
Tuesday, 24 November, 2009

Australian researchers, led by Dr Jeremy Henson at the Children’s Medical Research Institute (CMRI) in Sydney, have developed a new quick and easy assay that detects the characteristic behaviour of certain cancer cells and could lead to the development of a test for most cancer types as well as new targeted chemotherapy drugs.

Almost all cancers use one of two mechanisms to continue multiplying indefinitely. Most utilise the enzyme telomerase, discovered by Elizabeth Blackburn and her colleagues, which enables the cells to prevent the ends of their chromosomes from shortening as they continue to divide.

The other technique is 'alternative lengthening of telomeres' (ALT), which is used by around 10 to 15 per cent of cancers, including some aggressive brain and bone cancers.

Until now, detecting ALT activity was a laborious and time consuming process - taking up to three months - but with the new assay, ALT activity can be screened for in only a few days.

The assay detects partially single-stranded telomeric (CCCTAA)n DNA circles - called C-circles - in the blood. These C-circles are ALT-specific, thus indicating the presence of a cancer that uses the ALT mechanism.

Combining tests that detect the presence of telomerase with the assay for C-circles could lead to a single blood test that could rapidly screen for the presence of a majority of cancer types.

According to Henson, the assay could also aid in the discovery of ALT inhibitors, which could be used to develop drugs that kill the cancer without affecting normal cells.

"That's the longest shot, but I'm very optimistic," he said.

Finding ALT inhibitors has been a difficult process in the past, but with the new assay, the process can be sped up dramatically.

"In the next few months we should be able to screen hundreds of genes to see if they're involved in the ALT mechanism, as they could be potential drug targets," said Henson.

The research was published in the journal Nature Biotechnology.

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