New class of chemotherapy drugs for hard-to-treat cancers are on the horizon

Differences in the way cancer cells function are shining a light on the potential for a whole new approach to developing treatments.

In the future, researchers believe this could be particularly significant for cancers that are difficult to treat, such as pancreatic cancer or oesophageal cancer. Only 15 per cent of people diagnosed with oesophageal cancer survive for five years or more after diagnosis. In pancreatic cancer, the figure is a mere 3 per cent.

The outcomes of this research contribute to a growing field that aims to create tailor-made treatments for individual tumours, based on their unique characteristics.

In a study published in Nature, Professor Rob Goldin from the Department of Medicine at Imperial College London, working with a group in the Ludwig Institute in Oxford lead by Skirmantas Kriaucionis, has shown that the enzyme cytidine deaminase enables cells to recycle old DNA into new, to help cells divide and grow.

Cells do this by breaking DNA down into its component units called nucleotides, then putting them back together into new strands. However, cells that contain too much of the enzyme becomes overzealous recyclers allowing new DNA to be made from nucleotides that have been modified or damaged.

Professor Goldin said: “We are all familiar with recycling our household waste. What we’ve discovered is that these cancer cells are over-zealous recyclers who are putting rubbish in with their recycling which ends up damaging them.”

Scientists already know that when cells begin to accumulate too many damaged bases in their DNA, they will die. Now the researchers say they can capitalise on this defect to target and kill cancer cells.

Professor Goldin said: “Now we’ve discovered this difference we can begin to exploit it. We think it is possible to treat cancer by administering lots of damaged bases. Healthy cells will throw the bases away but cancer cells will try to recycle them, ultimately leading to their death.”

In this way the researchers believe they can develop a treatment that targets tumours but has fewer side effects for a patient.

Professor Goldin hopes that looking for other similar quirks in cancer cells will yield a whole new class of chemotherapy.

Professor Goldin said: “This is the clearest illustration, yet, that differences in the way normal and cancer cells carry out their internal housekeeping can be exploited to find a treatment that will target disease. Cancer is a complex set of diseases and there is no one simple answer. Based on this study, we think there may be many other differences in the way cancer cells function which could be targeted for new treatments.”

REFERENCE

Zauri et al (2015) “CDA directs metabolism of epigenetic nucleosides revealing a therapeutic window in cancer”, Nature 524, 114–118, doi:10.1038/nature14948