A hyper-personalised approach to stop tumours spreading
When a tumour spreads to another part of the body, the cancer enters a new, more advanced stage for that patient, and the disease often becomes more difficult to treat. For around one in every three women with breast cancer, these wandering or metastasising tumours cause problems in other organs, such as the lungs and liver or in the bones.
In Ireland alone, around 1,700 people are living with metastatic breast cancer, and tackling metastatic disease remains one of the big challenges for breast cancer research. With the support of Precision Oncology Ireland, Professor Leonie Young has been analysing the changes in tumours that enable them to spread. Today, she is the co-founder, along with Dr Damir Vareslija and Prof Arnold Hill of Probmet, a spin-out company from RCSI University of Medicine and Health Sciences, which is testing a new way of blocking the spread of breast cancer tumours.
“The aggressive tumours that spread tend to be what’s called plastic, which means they change and spread and become resistant to treatments, and we are interested in those changes,” says Professor Young, who heads the Endocrine Oncology Research Group at RCSI University of Medicine and Health Sciences.
Her hyper-personalised research with Precision Oncology Ireland analyses not only individual patients, but individual tumours within that patient. It zones in on the genetic differences between the original breast tumour and the tumours that make their home elsewhere in the body.
“We compare the primary tumour and the tumours that have spread or metastasised to a distant organ,” she says. “These changes that happen may be what allows the more distributed tumours to adapt to other parts of the body and to develop resistance to the treatment the patient is getting for the cancer.”
Together with surgeon Professor Arnie Hill, Professor Young set up the National Breast Cancer Biobank in 2006, which curates tissue from tumours along with clinical data, and makes them available for research. The biobank is now part of Precision Oncology Ireland.
“This biobank, and the patients who consented for their tumours to be part of the study, really enabled us to analyse what changes at a molecular level to tumours as they spread,” she says.
Working with scientists in the Precision Oncology Ireland network Professor Young was able to integrate various types of data from tumours to learn more about how the tumours were functioning.
“We worked with Professor Walter Kolch to use computational biology,” explains Professor Young. “This meant we could bring together deep sequencing information about DNA from tumours along with other, functional data, and find out the genes that were involved in regulating how that tumour behaved in that patient. Being part of Precision Oncology Ireland was really useful for this work, it connected us with a huge diversity of researchers, including mathematicians, molecular biologists and clinicians, and we were able to share skills and expertise across platforms,” she says. “This helped to move the bar on our research significantly.”
Professor Young is co-founder of Denmark-based Probmet, which is now developing a small molecule that can block a key receptor that is abundant on breast cancer cells that are spreading. “We are targeting the ability of tumour cells to communicate with new parts of the body, in a bid to stop it establishing new sites and growing there,” she says.
And while the hyper-personalised approach of comparing individual tumours from individual patients is currently an expensive approach, Professor Young believes that over time the price will fall and it will become a part of standard care.
“Being able to understand how tumours are behaving in an individual will mean that person can get treatments to fit their own situation,” she says. “And where you have a family history, it means we could be able to point to how a person can potentially stay a step ahead of a cancer where they have a high risk.”
Doing this research in precision oncology to inform future prevention and treatment of metastatic disease needs scientists and clinicians and patients working together, notes Professor Young.
“It’s motivating to work with the community in Precision Oncology Ireland,” she says. “We are coming from different backgrounds to work on the same goal, and we can all see the benefit.”