Searching for the Achilles Heel of paediatric cancer cells: Daffodil Day 2022
Posted on: 25 March 2022
To some, 20 years may seem like a long time to study one particular subject, but Professor Adrian Bracken has spent that time focussing on ‘cellular identity’ or what gives cells their distinguishing character. Adrian and his team in the Bracken Lab (established 12 years ago) in Trinity study the genes that regulate cellular identity; genes that are crucial in our developmental biology, but genes that can also sometimes mutate, with detrimental outcomes. One such mutation on the H3K27M gene causes a devastating, incurable childhood cancer, known as diffuse midline glioma or DMG (also known as Diffuse Intrinsic Pontine Glioma, DIPG). 10-12 children were diagnosed with DMG in Ireland last year.
By understanding the biology of the H3K27M oncogene and how it works, the Bracken Lab are discovering how the gene drives the cancer and identifying targeted therapies to treat patients.
Adrian (pictured) was the recipient of the Irish Cancer Society’s 2020 Cancers With Unmet Needs Translational Research Award. The award aims to provide funding for a translational research project that addresses an issue(s) in a cancer with an unmet need, that is a cancer that has a lack of effective treatment options and/or a lack of research capacity in the area. The award enabled Adrian and his research team to undertake important research focused on DMG.
DMG typically occurs in young children and is unfortunately not successfully responsive to chemotherapy or radiation therapy and has a median survival time of 1-2 years following initial diagnosis. The major unmet need for DMG patients is to identify effective treatment options.
Adrian explains the treatment challenges with this type of cancer: “Up until recently, treatment for DMG has really only been palliative which means trying to make the symptoms less severe for the child, but you are not really finding a treatment that is curative or stops the cancer.” He points out that the biggest challenge is that the cancer is in the brain, so surgery is really not an option. “What’s needed is more targeted therapies that can go in and get at the underlying cancer causing genes and stop the cancer in its tracks because chemotherapy and radiotherapy are not working, and surgery is not possible.”
Targeted therapies, or ‘precision oncology’ requires an understanding of the underlying genes that are causing the cancer. They then become the target. Adrian uses the example of the ‘Achilles Heel’ to describe his work:
You have the super warrior, but he has one weakness. And so the precision oncology approach takes that strategy where you are looking for and studying the cancer cells, the biology, the genetics and you are looking for what’s its Achilles Heel is, what’s its weak point? And you go after that.”
With regard to paediatric gliomas, Adrian says that ‘we know its strengths and its weakness, if we can block the oncogene (H3K27N) function, we are going after that, once you go after the function of that, it basically knocks the wheels from under it, it blocks its progress.
The importance of funding cancer research
Adrian expresses his gratitude for the support from the Irish Cancer Society. In the time since Adrian received the award (March 2021) there has been much progression in the Bracken Lab as they come up with new ways to treat this cancer. The award has allowed Adrian to employ a new research assistant whose project and work Adrian has high hopes for. He believes the benefit of the Irish Cancer Society support will really come over the next few years as new strategies to treat this deadly cancer are developed by his team.
Talk of research funding prompts Adrian to highlight the importance of people donating to Daffodil Day which will allow the Irish Cancer Society to provide bigger grants to researchers which can support the recruitment of more research staff, therefore increasing the chances of discoveries which will lead to better targeted treatments for patients.
Through the Irish Cancer Society award, Adrian and the team have been able to speak with families, patients, doctors and paediatric oncologists, allowing the team great personal insight and knowledge into the disease and its potential targeted therapies. The award has provided this support to have invaluable conversations beyond the lab, with those directly affected by DMG, both nationally and internationally.
The future of cancer research
Looking ahead to the next 5 – 10 years in cancer research, Adrian sees a transition from traditional therapies such as chemotherapy to more targeted therapies. He expects the language around newer therapies to become more established in the mindsets of nurses, doctors and patients, with a better understanding for patients of their targeted, more specific therapy for their particular type of cancer. This he feels is reassuring because through ‘precision oncology’ patients are getting the best treatments that are going to suit their disease, which is giving them the optimum outcome. He foresees a reduction in the negative side effects of traditional cancer therapies, as newer therapies target the cancer cells and not the normal, healthy cells in the body.
Adrian also hopes that people will perhaps be less fearful of cancer and the concept of people’ living with cancer’ might grow. He already sees a move towards a world where people will be able to get treated on an individual basis for the cancer type that they have and have better expectations for their outcome and at the very least, for living with the disease.
When asked to think about the impact of his research work over the last number of years, Adrian is rather self-effacing;
“I didn’t set out to in my career to cure cancer. I’m just a nerd, a specialist, a geneticist who is just interested in this group of genes. The fact that they are relevant in two or three cancer types is great, it’s very satisfying that we can bring our knowledge on this to do something really useful here.”
Adrian is an Associate Professor of Medical Genetics at Trinity College Dublin, Theme lead of Cancer Genomics and Precision Medicine at the SFI Centre for Research Training in Genomics Data Science and Precision Medicine Research Theme Lead at the Trinity St. James’s Cancer Institute.
More information
The Bracken Lab at Trinity: http://www.gen.tcd.ie/bracken/
Adrian’s IRISH CANCER SOCIETY award here.
Adrian’s recent published study in the journal Nature Genetics here.