Dundee discovery opens paths to new cancer treatments
Published on 6 December 2023
Cancer Research UK-funded scientists in Dundee have discovered how some cancer drugs can target the disease while sparing healthy tissue.
The discovery paves the way to finding new and kinder treatments which are more effective at killing cancer and have fewer side effects for patients.
Each year around 34,100 people are diagnosed with cancer in Scotland. With around 16,300 Scots sadly losing their lives to the disease annually, finding new ways to tackle it is vital.
Cancer treatments such as chemotherapy can be difficult for patients as the treatment usually affects all cells, not just the cancer cells, and can make some people feel unwell.
Now, thanks to funding from Cancer Research UK, a team at the University's School of Medicine believe their findings explain how a class of anti-cancer drugs is able to effectively target cancer cells while leaving healthy cells relatively untouched.
The research, published in Molecular Cell, focused on established cancer treatments known as CDK4/6 inhibitors which work by stopping cancer cells from replicating and preventing them from producing more cancer cells.
Cancer Research UK-funded scientists were key in demonstrating the effectiveness of CDK4/6 inhibitors to treat breast cancer and these drugs have now been used for a decade to treat breast cancer patients whose cancer has spread to other parts of the body. However, it was unclear exactly how these drugs were specifically able to target cancer cells.
In lab tests, the Dundee team found that CDK4/6 inhibitors stopped both cancer cells and healthy cells from dividing, but the cancer cells specifically continued to grow in size. In the end, these cancer cells became so large that they could not function and permanently stopped replicating.
The team established that the cells continued to grow because of the oncogenes, which are the faulty genes which cause cancer in the first place.
Senior author, Dr Adrian Saurin, said, “The answer was quite simple in the end. Oncogenes cause cancer cells to grow and divide uncontrollably, so when you stop their division with CDK4/6 inhibitors, they are then programmed to just grow excessively. This overgrowth soon becomes toxic for cancer cells.
“The really exciting finding is that these drugs can turn oncogenes against cancer cells. That could explain why they produce toxic effects in cancer cells rather than healthy cells.”
A second team, involving researchers from the University of Dundee and the Medical Research Council Laboratory of Medical Sciences at Imperial College London, sought to find out why cancer cells stopped dividing permanently when they became too large.
They discovered that being too large triggers chemical stress which prevents these massive cells from replicating.
Dr Tony Ly, from the University's School of Life Sciences, added, “A surprising finding was that these CDK4/6 inhibitors made cancer cells become much larger than they should be.
“We showed that being too large produces a cellular stress response causing cells to enter senescence, a protective type of dormancy that prevents cancer cells from further dividing.”
The Dundee researchers hope that this work will allow further treatments to be identified which also target these processes.
Although this research specifically looked at a drug used to treat metastatic breast cancer, the findings could support research on a wide variety of cancers and unlock the path to kinder, more effective treatments.
This work was funded by Cancer Research UK, the Wellcome Trust and the Royal Society.
Dr Catherine Elliott, Director of Research at Cancer Research UK, said, “Our scientists laid the foundations for the development of CDK4/6 inhibitors more than 30 years ago and these new findings into these drugs work could see future generations having far better outcomes than in previous decades.
“This kind of discovery is the bedrock of cancer research. Long term innovative research seeking new approaches to treating cancer is the key to unlocking a better future for cancer patients.”
The paper, “Oncogenic signals prime cancer cells for toxic cell overgrowth during a G1 cell cycle arrest,” is published in Molecular Cell and is available here: https://doi.org/10.1016/j.molcel.2023.10.020
The paper, “CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence,” is published in Molecular Cell and is available here: https://doi.org/10.1016/j.molcel.2023.10.016
*Based on the average annual number of new cases of all cancers (ICD10 C00-C97, excluding C44) diagnosed in Scotland in the years 2017 – 2019.
**Based on the average annual number of deaths from all cancers (ICD10 C00-C97) in Scotland in the years 2017-2019.
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