Research: Target DNA ‘Shoelaces’ to Treat Cancer

February 03, 2012 - News Release

Doctors and drug companies looking to treat cancer by targeting DNA’s “shoelaces” might gain support from a new study involving researchers at the University of Guelph.

The study shows that human tumours rely on the maintenance of shortened telomeres, or the protective ends of chromosomes — evidence that may help in developing anti-cancer drugs that target those structures, said Prof. Dean Betts, an adjunct professor in the Department of Biomedical Sciences at the Ontario Veterinary College.

The study, including key experiments done at U of G, is described in an article published online Feb. 2 in Cell Reports .

The study was conducted by Lea Harrington and other researchers at the University of Toronto and the University of Edinburgh as well as Betts and U of G adjunct biomedical sciences professor Chandrakant Tayade.

Telomeres are short DNA stretches that help protect the ends of chromosomes, like plastic tips preventing shoelaces from fraying. These stretches shorten with repeated cell divisions, leading the cell to age and eventually die.

In cancer cells, the telomerase enzyme helps to keep telomeres from shortening even more. That enables cells to divide even when the normal brakes on cell division fail, as in cancer.

Earlier, scientists had shown that telomere maintenance was needed for cancer to develop, but they had not tested whether it was needed for cancer cell growth when telomeres are long.

At Guelph, the researchers transplanted human tumour cells with longer or shorter telomeres — and with or without telomerase — into genetically engineered mice.

Human cells lacking telomerase but with long telomeres formed tumours in mice. No tumours formed when transplanted human cells had short telomeres and lacked the enzyme.

“The results help explain the better long-term prognosis of some telomerase-negative pediatric cancers and also support tumour treatment with anti-telomerase therapy,” said Betts. Several companies are working on cancer-fighting drugs that target this enzyme.

Their work also underlines the widespread role of telomeres in many kinds of cancer, he said. Anti-telomerase treatments might prove an all-purpose tool, unlike drugs tailored to specific tumour types or individual genetic differences.

Such drugs might kill certain types of normal cells with active telomerase as well as tumour cells. But radiation and chemotherapy also kill normal tissue around the tumour, said Betts, whose father recently underwent treatment for lung cancer.

“Telomerase therapy would have similar effects, but then possibly its potency will help eradicate cancer faster and reduce side effects by having patients on radiation or chemotherapy for a shorter time,” said Betts, who joined the Department of Physiology and Pharmacology at the University of Western Ontario in 2008.

Tayade, who was a Guelph post-doc and faculty member before joining the Department of Biomedical and Molecular Sciences at Queen’s University in 2009, said, “There are serious pharmacological interventions we can target.”

For media questions, contact Communications and Public Affairs: Lori Bona Hunt, 519-824-4120, Ext. 53338, or lhunt@uoguelph.ca, or Shiona Mackenzie, Ext. 56982, or shiona@uoguelph.ca.

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