Targeting treatments to cancer cells is a key goal of childhood cancer research. After all, why wouldn’t you want your treatment to only harm the thing you want to fight?
Think of it like gardening - you wouldn’t want to spray weed killer over your entire garden, harming your lawn and flowers, when you are trying to kill a few weeds. While weeds may be easy to see in a garden, tiny cancer cells are much harder to find when hiding in the body. This is why many traditional cancer treatments like chemotherapy treat the whole body, which can then cause side effects like hair loss or sickness.
Researchers are working hard to change this, developing treatments that target cancer cells directly. Some great new targeted treatments are already available for children, like CAR T-cell immunotherapy, and older examples exist like imatinib and rituximab.
However, many of these targeted treatments are only used for very specific types of cancer or cases. Targeted treatments are also often specific to certain genetic errors, leaving many children without access to these kinder options.
How can we target cancer?
Cancer cells are not like invading viruses or bacteria - they begin as healthy cells. This makes them a lot harder to separate from normal cells.
To design treatments that attack cancer cells without hurting healthy cells, researchers must find out what makes cancer cells different and what makes them vulnerable. Often, this means looking at the cancer cell proteins.
Cells make proteins using the instructions provided by their genetic code. Proteins control most of what goes on in cells, from how they behave to how fast they grow. Cancer cells can behave differently because they have errors in their genetic code, meaning they have abnormal proteins or the wrong amount of certain proteins. Researchers can use these differences to target treatments.
Targeted treatments for lymphoma
Professor Suzanne Turner and her team at the University of Cambridge are working on a new treatment for children with anaplastic large cell lymphoma (ALCL).
Professor Suzanne Turner
She said: “Most of the chemotherapy drugs we use to treat children with lymphoma, a cancer of the immune system, are toxic not only to the cancer cells but also to other cells in our bodies. This leads to the nasty side effects we all associate with chemotherapy such as hair loss, tiredness and nausea.
In Suzanne’s lab, they are investigating a treatment that will target a protein called METTL3, which has been shown to help other blood cancers grow. The Little Princess Trust-funded project finished in early 2024 and was originally led by Dr Isaia Barbieri. Suzanne’s team continues to work with Isaia at his new lab at the University of Turin in Italy. Together, they have been looking at ‘turning off’ the METTL3 protein with new drugs called METTL3 inhibitors.
Dr Liew Jun Mun, a key member of Suzanne's lab team.
Suzanne explained: “METTL3 is a protein found in normal healthy cells but is also hijacked by cancer cells. METTL3 makes changes to the way our genetic code is interpreted and in doing so, can change the behaviour of cells. METTL3 inhibitors counteract this activity and can prevent the growth of cancer cells.”
The project is particularly focused on children that have ‘ALK-positive’ ALCL, which is when the cancer cells make the ALK protein to help them grow. This can be difficult to treat for around 15% of patients, despite new treatments called ALK inhibitors that stop this protein from functioning in cancer cells.
Suzanne said: “Children diagnosed with ALK+ ALCL have a relatively good prognosis and there are lots of treatment options available including a newer generation of drugs called ‘ALK kinase inhibitors’. However, we do not fully understand how best to use these drugs in the clinic and when they have been used to treat children, the disease can return when stopping the drug.
“We might be able to prevent this from happening if we combine different drugs which work in a complimentary manner. METTL3 inhibitors provide us with this opportunity as they have a different mechanism of action to ALK inhibitors.”
Suzanne and Isaia hoped to find out whether the METTL3 inhibitors could be used alongside the ALK inhibitors to cure more children and young adults with fewer side effects than standard treatments.
A potential combination treatment
Using ALCL cells grown in the lab, and models that mimic real patients’ cancers, the researchers were able to show that METTL3 is important for ALCL survival and growth. They were also able to test METTL3 inhibitors, both alone and in combination with ALK inhibitors.
Suzanne said:
Our data show that when we combine ALK kinase inhibitors with METTL3 inhibitors, the two drugs work together in a complimentary way to kill the cancer cells. This means that lower doses of both drugs can be used together, having a stronger effect than higher doses of either drug alone. This suggests that children with ALCL might benefit from a combination of these drugs.
Using both targeted drugs together at a lower dose should mean that the treatment does less damage to healthy cells, meaning that children have fewer side effects. Now that Suzanne and Isaia’s labs have shown the potential of this treatment for ALCL patients, Suzanne will begin research to form the foundations for future clinical trials. The goal is to bring a new treatment option for young patients as soon as possible, whilst ensuring that it is safe and effective.
She added: “METTL3 inhibitors have not yet been approved for use in adults or children and so a clinical trial is required first to test the safety of these drugs and to find the right doses. This is currently happening for adults through a phase one study for advanced cancers. It will be a few more years before the results of this trial are known and therefore whether it is safe to trial this drug for children.”
Ellie Ellicott is CCLG’s Research Communication Executive.
She is using her lifelong fascination with science to share the world of childhood cancer research with CCLG’s fantastic supporters. You can find Ellie on X: @EllieW_CCLG
