Professor Nives Pećina-Šlaus, Head of the Laboratory of Neuro-oncology at the Croatian Institute for Brain Research (University of Zagreb) explains how research conducted in her group can impact future brain tumour therapy.
The genetics of cancer (called Cancer Genomics) is nowadays one of the fastest expanding medical specialities and this vast knowledge is now used to develop novel and efficient therapeutic methods. We now understand that cancer is not a single disease but rather a collection of diseases with diverse genetic profiles. Being caused by mutations in our DNA, cancer can be considered a genetic disorder in which the normal control of cell growth is impaired. The mutated genes can impact a variety of vital cellular processes:
Some of these “cancer genes” also affect how signals from outside of the cell talk to the cell headquarter: the nucleus. These constant and complex signals form a network collectively called “signalling pathways”. The Wnt (pronounced “wint”) signalling pathway is one of such pathways and relays many essentials information for the cell. Wnt signalling is critical in human brain development and often impaired in cancer patients, especially with certain types of brain tumours.
Professor Nives Pećina-Šlaus and her group recognise that the knowledge on altered Wnt signalling in tumour cells is an important step forward understanding brain tumour origin. The group is studying Wnt signalling as part of a project financed by the Croatian Science Foundation. The main signalling protein of the pathway is β-catenin and constitute a potent cancer-causing gene. The results of their research suggest that molecular changes of this pathway are implicated in two different types of brain tumours. Also, the classical Wnt signalling pathway has a tight link with a complex process by which cells lose their function within the body and start to move away from their original home.
This process of loss of specialisation of cells during cancer development occurs in many types of cancer and is called the “epithelial-to-mesenchymal transition” or EMT for short. In this complex cascade of molecular events, tumour cells, that were previously immobile and part of the tissue architecture become mobile and can go to distant organs, becoming invasive. Her postdoctoral fellow, Dr Anja Kafka and doctoral student Anja Bukovac, are working on finding the role of several different genes in brain tumour formation and progression in relation to EMT. This is important for the characterisation of markers that will help us in diagnostics and the design of future treatment weapons indicates Pećina-Šlaus. The success of any effective therapeutic approach will need to consider specific molecular changes in the Wnt signalling cascade to avoid this exodus of rogue cells and therefore cancer progression.
The Laboratory of Neuro-oncology (in collaboration with the Clinical Hospital Centres in Zagreb and Sisters of Mercy) is also actively involved in the creation of a brain tumour tissue bank, consisting of a collection of biopsies of brain tumours to be used as a vital research resource for scientists interesting in studying the origin of brain cancer.
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