New anti-cancer drug linked to DNA damage

University of Dundee researchers have discovered that a new type of anti-cancer drug that stops tumour cells from dividing can have long-lasting effects by causing “catastrophic” DNA damage to cells.

This is a completely unexpected finding that may have significant implications for future treatments.

CDK4/6 inhibitors were recently licenced to treat the most common subtype of breast cancer due to their ability to stop tumour cells dividing. An important feature of these drugs is that their effects can last a long time after treatment has stopped, but the reasons for this were unclear. A team, led by Dr Adrian Saurin at the University’s School of Medicine, set out to clarify the issue.

Unexpectedly, they found that when CDK4/6 treatment was stopped the cells started to divide again almost immediately but were unable to properly replicate their DNA when doing so. This caused their DNA to become damaged and for the cells to abort division and stop growing altogether.

Dr Saurin and his colleagues believe this action may help to explain why these drugs have long-term beneficial effects in patients. If the results of this early-stage lab work are verified in patient samples then it raises the possibility of doctors being able to use these drugs more effectively in future, both in the treatment of breast cancer or potentially in other tumour types.

“CDK4/6 inhibitors have recently revolutionised the treatment of the most common subtype of breast cancer but the fact that these drugs can cause catastrophic DNA damage was completely unknown and unexpected,” explained Dr Saurin.

“When the DNA is damaged inside cancer cells they can stop growing permanently, and this could be very important in the case of CDK4/6 inhibitors. These drugs work in a very general way to stop cancer cells dividing and so, in theory, they could also be beneficial for a wide variety of other tumour types.

“Our results now need to be followed up in clinical samples, but if DNA damage is also found to occur in patient tumours then this would be very exciting because it may provide new ideas for treatment.

“For example, combination treatments could potentially be designed to create more extensive DNA damage, or tumour types could be identified that are the most sensitive to this damage. Scientists have been racing to find out which other tumour types may respond to these drugs, and whether they should be used alone or in combination with other drugs. There are currently over 100 ongoing clinical trials to test all these questions, and our findings provide another potential avenue to explore as we attempt to discover the full potential of these inhibitors.

“This is still very early-stage research, but we hope our findings could eventually help us to identify the patients most likely to benefit the most from CDK4/6 inhibitor drugs.”

The research, published today in The EMBO Journal, was funded by The Medical Research Council, Tenovus Scotland, and Cancer Research UK.

Michelle Mitchell, Chief Executive of Cancer Research UK, said, “Our scientists laid the foundations for the development of CDK4/6 inhibitor drugs over 30 years ago. These drugs are now being used to help people with advanced breast cancer have more quality time with their loved ones.

“While this is very early-stage research and further studies are needed, it could help boost the treatment effects of CDK4/6 inhibitors and open up the possibility that these drugs can be used in combination with other therapies to treat other types of the disease.

“Unpicking cancer’s complex mechanisms is the first step on the journey to new treatments. Just as past discoveries have laid the foundation for current successful treatments, new research like this will be at the heart of progress that will help people live longer and could save lives.” ​