Telomeres are DNA sequences found at the ends of chromosomes that play a key role in controlling the life span of cells. With every cell division, telomeres get a bit shorter until eventually they become so short that the enzymes that copy DNA for cell division no longer work properly and the cell stops dividing. In a sense, telomeres function as a kind of counting mechanism that regulates how many times a cell can divide.
In contrast to normal cells, cancer cells divide continuously and uncontrollably. Scientists know that cancer cells produce an enzyme, called telomerase, which prevents telomeres from getting too short so cells can keep dividing. Telomerase is not used by healthy cells, and has been identified as a logical target for anticancer therapeutics.
However, recent studies indicate that for this therapy to be effective, telomeres must be in a critically short state, requiring an extended treatment duration that can lead to drug resistance and other problems.
Dr Hiroyuki Seimiya from the Japanese Foundation for Cancer Research in Tokyo and colleagues examined what happens to cancer cells when telomerase inhibition is combined with inhibition of an enzyme called tankyrase 1 that is involved in making telomeres accessible to telomerase. The researchers found that both tankyrase 1 activity and telomere shortening decrease the effects of telomerase inhibitors.
Importantly, tankyrase inhibition enhanced telomere shortening upon treatment with a telomerase inhibitor and accelerated cancer cell death.
“This study provides insight into strategies for telomere-based molecular cancer therapeutics,” said Dr Seimiya. “We expect that inhibition of tankyrase 1 will compensate for incomplete inhibition of telomerase. Consequently, this strategy would shorten the time period of drug treatment that is required for the onset of telomere crisis and reduce the potential risk of acquired drug resistance.”