Cancer cells can resist treatment by displaying plasticity and becoming motile. “We can now recover circulating tumour cells while they are still alive, allowing us to study how they function,” says Professor Kirsi Ketola.
Ketola was appointed Professor of Medical Biochemistry at the University of Eastern Finland in the spring. Her research focuses on how cancer cells become resistant to treatment, especially in prostate cancer, and how this could be prevented. A new cancer laboratory to be established in Kuopio will also provide new insights into metastasis formation.
Cancer cell plasticity poses a challenge
The growth of prostate cancer depends on male hormones, or androgens, so it can be controlled with medicines that inhibit the activity androgens or androgen receptors. However, treatment often stops working when cancer cells become drug-resistant. “This may be due to a variety of mechanisms, which current technologies allow us to investigate at the single-cell level in a tumour sample.”
A particular focus is cancer cell plasticity, whose broader significance in cancer has begun to emerge in recent years. “Normally, stem cells differentiate into cells of different tissues, and this differentiation is not reversed. Cancer cells, however, can revert to a stem cell-like state in which they evade the effects of treatment.”
“Cancer cells that have become stem cell-like can also differentiate in new directions, such as into neuroendocrine cells. These cells do not have androgen receptors, so the medicines currently available are not effective. Neuroendocrine prostate cancer rapidly leads to death.”
The Cancer Cell Plasticity Research Group within the Ketola Lab investigates factors that lead to these changes. For example, a drug that inhibits androgen receptor activity was found to activate the SIX2 protein, which may increase cancer cell plasticity. Normally, SIX2 is active during embryonic development, where it maintains cells’ ability to differentiate. Silencing it reduced the stem cell-like properties of cancer cells.
Another study showed that androgen deprivation therapy causes cancer cells to begin expressing the DPYSL5 protein, which normally regulates the development of brain cells. In cancer cells, it promoted stem cell-like, neuroendocrine and neuron-like features. Reducing DPYSL5 returned the cells to a state in which treatment can have an effect. “Our aim is to continue studying both SIX2 and DPYSL5 as new targets for drug development.”
As prostate cancer progresses, the tumour microenvironment also changes. The Ketola Lab has observed, among other things, that stiffening of the extracellular matrix and an increase in pro-inflammatory immune cells, M1 macrophages, affect cancer progression.
Recently, researchers have become interested in how cancer exploits the surrounding nervous system in order to grow. Cancer cells that have acquired neuron-like features grow protrusions that allow them to invade their surroundings. “We do not yet know whether these protrusions also help the tumour to establish connections with nerve cells.”
Drug testing with circulating tumour cells
In Kuopio, there is close collaboration between the university’s Multidisciplinary Cancer Research Community, Kuopio University Hospital and the Biobank of Eastern Finland, which is responsible for collecting patient samples. The new cancer laboratory to be established in Kuopio will further expand research opportunities and make the latest analytical methods available to companies as well. The Living Biobank – Cancer Laboratory SYLI project is funded by the European Regional Development Fund. Ketola serves as the principal investigator of the project.
A unique service model is being developed for the cancer laboratory. It will cover the entire sample workflow, from processing a biobank sample ordered by a client, for example with a drug compound, to its microscopy analysis and bioinformatics analysis of the results. The model is currently being piloted with several companies.
Among other things, the cancer laboratory will carry out analyses of living cancer cells. “Similar technology is not yet available anywhere else in Northern Europe,” Ketola says.
“We can isolate circulating tumour cells from patients’ blood and use them to study how cancer attempts to spread. These are precisely the highly motile cells that form metastases, which is why they are also of interest for testing drug treatments.”
Cells can also be transferred into zebrafish to study the development of metastases and the effects of drugs.
Circulating cells complement research carried out using tumour samples and various patient-derived cell models. For example, the Ketola Lab also receives prostate cancer samples from an extensive network of collaborators around the world.
Kirsi Ketola
Professor of Medical Biochemistry, University of Eastern Finland, 1 April 2026–
- MSc, Biochemistry, University of Turku, 2008
- PhD, Biochemistry and Molecular Biology, University of Turku, 2012
- Title of Docent in Molecular Medicine, University of Turku, 2023
Key roles
- Research Director, University of Eastern Finland, 2024–2026
- Director of the Cell and Tissue Imaging Unit, University of Eastern Finland, 2021–
- Academy Research Fellow, University of Eastern Finland, 2019–2024
- Senior Researcher, University of Eastern Finland, 2017–2019
- Postdoctoral Researcher, University of British Columbia, Vancouver, Canada, 2012–2017
For further information, please contact:
Professor Kirsi Ketola, [email protected], https://uefconnect.uef.fi/kirsi.ketola/
