Glioma is a broad category of brain tumours from glial cell. Amongst them, glioblastoma multiforme (GBM) is the most malignant and aggressive subtype in adults, having an incidence of 2-3 per 100,000 adults per year and affecting more males than females up to a ratio 3:1. This subtype is a grade 4 tumour, with fast growth rate, and sometimes spread to other parts of the brain. Current treatments include surgery, radiotherapy and chemotherapy; however, prognosis of most glioma is not optimistic, with survival rate normally ranging 14-18 months, with only around 10% of the patients living up to 5 years after diagnosis. This is partly due to the existence of glioma ‘cancer stem cells’ (CSCs), a subtype of tumour-initiating cells found in glioma with stem cell-like properties and resistant to conventional therapeutic treatments, being the cause of most relapses after treatment. Its aggressiveness is due to the complexity and the lack of full understanding of the biochemical nature and mechanisms of these type of tumours.
Recently, the importance of the mechanical properties of tissues in health and disease has become evident and has opened a new research field in biology. It is known that the mechanical environment of tumours is very hard, and that tumour cells overexpress proteins that respond to these changes in the mechanical properties, named mechanoreceptors. Stretch-activated cation channels (SACs) are a broad family of mechanosensitive channels that when activated by stretch, allows the influx of cations. Piezo1 –also known as FAM38A-, belongs to this subtype of mechanoreceptors.
This project is focused on understanding the importance of the mechanical properties of brain tumour environment and investigating new therapies tackling these changes. It has been observed that tumour cells contribute to the stiffening of their surroundings, and we have studied that when tumour cells sense these mechanical changes, it contributes to the progression of the cancer. Thus, our main objective is to fully understand why it happens and to develop new therapeutic strategies that could help combat gliomas, so that later on they could be translated into the clinic for the patients to benefit from them.
