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ASCO: Telomeres and Cancer


At ASCO this week, Nobel laureate Elizabeth Blackburn chaired session during which she presented her work on telomeres and cancer. Telomeres, the regions of DNA at the ends of chromosomes, protect chromosomes from deteriorating or fusing with one another. When telomeres erode away, cells die, Blackburn said. Telomerase, the enzyme that continually adds DNA to the ends of telomeres to replenish them, has been implicated in cancer, as it makes cells "immortal" and allows them to grow out of control. But by mutating telomerase, researchers can make those cells mortal, Blackburn said. If the enzymatic activity of telomerase is inhibited, cancer cells gradually stop growing and start dying — some companies are working on drugs to do just that. But researchers are starting to find that if telomerase is knocked down completely, instead of merely inhibiting it, there is a rapid death of cancer cells, Blackburn said. And because the telomerase is being knocked down, but not knocked out, there is no telomere shortening in normal cells. The knock-down rapidly down-regulates cell cycle and tumor progression genes, including glucose metabolism genes. Recent studies have shown that rare telomerase mutations that cause telomere shortening in normal cells also cause diseases, like various cancers or diabetes — which studies have also linked to cancer, Blackburn said. Some studies have shown an association between short telomeres and cancer incidence and mortality, she added. In studies conducted in conjunction with psychologists, Blackburn has found that chronic psychological stress has an impact on telomere length. Chronic stress also raises levels of the stress hormone cortisol which, again, depletes telomerase, leading to telomere shortening in normal cells. Therefore, Blackburn said, in addition to drug companies developing ways to treat cancer through the telomeres, clinicians can help their patients prevent cancer by advising them to "limit psychological stress" as well as advising them to eat healthy and stop smoking or get the HPV vaccine.

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