Cancer's deadly calling card has always been its cells' ability to replicate with abandon. Scientists continue to seek effective means of destroying cancer cells, while at the same time, protecting the healthy cells of the body.
New research may have found a way to do just that. By stripping the malignant cells of their immortality.
Cancer cells don't behave like normal cells. Each time a normal cell divides, it must duplicate its DNA in order to produce a new cell. The DNA is packed inside the cell's chromosomes, so each time the cell divides, the chromosomes are replicated.
But over time, mistakes are made. The ends of the chromosomes are protected by telomeres - repetitive nucleotide sequences that form a cap over the ends of the chromosomes. But as our cells divide and age, the telomeres shorten. That's because the enzyme that maintains the telomeres, known as telomerase, turns off. Without the enzyme, the telomeres continue to fray, leading to the eventual death of the cell.
Cancer cells are different. They are immortal. The enzyme within cancer cells does not shut off, which keeps the telomeres from shortening and allows the cells to keep on dividing. And it's this unrestrained cellular division that allows cancer to sabotage the body and kill off its host.
But scientists at the Spanish National Cancer Research Centre (CNIO) have developed a means of stripping cancer cells of their immortality by "uncapping the telomere."
"Telomere uncapping is emerging as a potential mechanism to develop new therapeutic targets for lung cancer," mention the authors with equal contribution in EMBO Molecular Medicine; Maria Garcia-Beccaria, Paula Martinez and Marinela Mendez, from the CNIO Telomeres and Telomerase Group, led by Maria Blasco, who is also an author in the article.
By targeting the six-protein complexes on the telomere, known as shelterins (since they shelter the telomere), researchers were able to block the action of one specific shelterin, TRF1. Without TRF1, the telomeres lose their protection and the cancer cells suffer cellular death just like normal cells.
"TRF1 removal induces an acute telomere uncapping, which results in cellular senescence or cell death. We have seen that this strategy kills cancer cells efficiently, stops tumour growth and has bearable toxic effects," Blasco says.
The team has been able to inhibit the TRF1 in two ways: through genetic manipulation, where the gene was physically removed from mice used in the study; and using chemical compounds developed by the CNIO Experimental Therapeutics Programme.
"We've shown that we can find potential drugs able to inhibit TRF1 that have therapeutic effects when administered orally to mice," Blasco says.
And since the therapy is effective in mice, we can look to the future for its application in humans.
