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Blocking a protein molecule makes aggressive brain tumours more sensitive to radiotherapy and chemotherapy
Every year, around 8,000 people in Germany are diagnosed with a brain tumour. One of the most common and malignant variants is glioblastoma, which is considered particularly aggressive as the tumour cells grow quickly and migrate into the healthy brain. The chances of survival are often low, ranging from a few months to a year and a half. Researchers at the Dresden University Medical Centre and the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) want to change the biological cell properties of glioblastoma so that they become more sensitive to therapy. New findings on a specific protein molecule could help here.
24/04/2023
„The treatment of glioblastoma is difficult“, explains Prof. Nils Cordes, Head of Radiation Biology at the National Centre for Radiation Research in Oncology – OncoRay, which is jointly funded by the Faculty of Medicine and the Carl Gustav Carus University Hospital at TU Dresden and the HZDR. Surgery is not without risk because the tumour tissue is surrounded by sensitive brain structures. This also requires a very cautious approach to radiotherapy in order to exclude tissue damage in the surrounding area as far as possible.
„Our radiation options and the combination of therapies improve the chances of recovery from cancer“, explains Prof. Mechthild Krause, Director of the Clinic and Polyclinic for Radiotherapy and Radiooncology and Director of the OncoRay Centre. „Our scientific work is therefore characterised by a high level of dynamism in order to explore the many perspectives for gentler and more effective treatment strategies for the therapy and research of tumour diseases.“ The Director of the Clinic and Polyclinic for Radiotherapy and Radiation Oncology and Dean of the Medical Faculty of the TU Dresden, Prof. Esther Troost, adds: „This is where proton therapy, established in Dresden as one of only a few locations in Germany, comes into play as a particularly precise radiotherapy procedure that has developed enormously in recent years and is used for curative-intended radiotherapy.“
One possible route for gentle radiotherapy is via the extracellular matrix. For over 20 years, a research group at OncoRay has been working on this protein, which is distributed differently throughout the body. The cells attach there and give everything a structure - like an adhesive. This protein also plays a part in how cell functions, such as cell division or migration, are controlled in the organism.
Tumour cells and other, non-degenerated cells in a tumour produce such matrix proteins to a large extent. This means that the matrix in the normal brain is completely different from that in a glioblastoma," explains Cordes. The reason for this is still unknown. „Our approach is to block or down-regulate the receptors on the cells that enable them to attach to the matrix.“ This is possible, for example, through the use of antibodies or peptides. They can weaken or deactivate the connection between cells and matrix. This results in the tumour cells surviving less well after radiotherapy, chemotherapy or molecular therapy.In the current study, the researchers focussed on the surface protein integrin α2. Integrins connect cells with other cells and are responsible for cell integration into the matrix. In their work, they were able to show that the inhibition of integrin α2 significantly reduces the survivability of tumour cells during combined radiotherapy and chemotherapy. It is particularly important to look at the effect of this combination of radiotherapy and chemotherapy because this treatment method is standard for many patients today. A lack of integrin α2 also inhibits tumour growth. This could have a positive effect on the chances of survival for those affected. Further studies have also suggested that the approach could also be promising for head and neck tumours. The extent to which there are advantages in the treatment of other types of cancer remains to be seen in the future, as there is still very little work on integrin α2 worldwide.Taking a closer look at proteins in cancer therapy is a point that will become increasingly important in the future. So far, science and clinics have focussed on genetics, but it is only one component among many others, such as proteins. In an earlier study, the team therefore took a closer look at the composition of the cellular matrix in glioblastomas of different patients. A large proportion consists of collagens," explains Cordes. Integrin α2 is part of a collagen integrin. „There is therefore a good chance that we will find new solutions through intensive study of the proteins.“
„This is where the close links between research and clinical practice come into play, of which this work is a living example,
adds Prof Michael Albrecht, Medical Director of the Carl Gustav Carus University Hospital Dresden. „Only through close cooperation between research groups can we develop perspectives for treatment approaches to cancer.“
Now we need to check whether the positive results on integrin α2 are also reflected in the effects of a combined therapy. In a next step, we want to find out in laboratory experiments how efficient the use of integrin α2 inhibitors is in combined radiotherapy and chemotherapy,
says Nils Cordes, looking ahead to a future task for his group.
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