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Some types of cancer produce cells that are not as picky as ordinary, correctly functioning cells in the nucleosides they are willing to incorporate into their DNA during repair and replication. Researchers here propose that by introducing a suitably altered nucleosides into tissues it should be possible to produce DNA in cancer cells that will cause them to destroy themselves. Other cells in the body will be unharmed by the treatment. This is still in the early conceptual stage of development, however; it remains to be seen what hurdles lie ahead in the development of a practical therapy built on the idea:

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. But 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.

Cells are thrifty when it comes to synthesizing new DNA. In addition to making new nucleotides, they recycle chemical parts from the DNA of dying cells, or DNA that we ingest in our diets. However, one of the four types of nucleotides in DNA - the 'C' in genetic sequences - is often chemically modified. These chemical modifications, which are called epigenetic changes, are important for controlling genes and need to be in the correct places in DNA for cells to function normally. If the epigenetic modifications are on the wrong C nucleotides, they could make cells cancerous or kill them.

The enzymes that recycle nucleotides are highly specific. They don't use the modified nucleosides, so the new DNA is epigenetically 'clean.' However, when they looked at the recycling process in cancer cell lines, researchers discovered that some of the cancer cells are able to transform these nucleosides, allowing incorporation into new DNA. This process often kills the cells. It was the cancer cell lines that expressed unusually high levels of a protein called cytidine deaminase (CDA) that made this mistake in recycling. CDA is often overexpressed in certain tumor types, including pancreatic cancer. "It has been suggested that CDA inactivates cytidine analogues that are already used in the clinic to treat some blood and pancreatic cancers. In a strikingly reverse scenario, the nucleosides that we used in our study are relatively harmless until they encounter CDA, which converts them into hostile cytotoxic agents." The researchers will likely continue to investigate this new avenue for 'epigenetic' drugs as cancer therapies.

Link: http://www.ludwigcancerresearch.org/news/modified-dna-building-blocks-are-cancers-achilles-heel