Recycled DNA building blocks are cancer's Achilles heel. Normal cells have highly selective mechanisms to ensure that nucleosides - the chemical blocks used to make new strands of DNA - don't carry extra, unwanted chemical changes, finds Ludwig Cancer Research scientists.
But they also found that some types of cancer cells aren't so selective. These cells incorporate chemically modified nucleosides into their DNA, which is toxic to them. The findings indicate that it might be possible to use modified nucleotides for specific killing of cancer cells. Lead author Skirmantas Kriaucionis said that they sought to find out what happens to these modified bases when DNA is recycled, and were excited that their biochemical analysis uncovered "loopholes," which could hopefully be exploited for intervention in cancer.
Exploiting the unexpected killing of cancer cells by epigenetically modified nucleotides demonstrated in a model system that modified nucleotides can be used as a specific anti-cancer agent. Kriaucionis said that it has been suggested that CDA inactivates cytidine analogues that were already used in the clinic to treat some blood and pancreatic cancers. In a strikingly reverse scenario, the nucleosides that they used in their study were relatively harmless until they encountered CDA, which converted them into hostile cytotoxic agents.
The researchers will likely continue to investigate this new avenue for "epigenetic" drugs as cancer therapies. The study is published in the journal Nature