Expression of stem cell factor & its receptor in meningiomas

1-year studentship July 2005-June 2006


Investigator: Dr Federico Roncaroli, Kevin O’Neill

Lay summary: About 15-20% of meningiomas have an aggressive behaviour causing severe morbidity to patients because of their tendency to local recurrences. Radical surgery increases the relapse-free survival and radiotherapy gives advantages in controlling residual tumour if excision is incomplete, but both treatments become ineffective when local recurrences or dissemination occur. No effective medical treatment is currently available. The aim of this one-year project is to explore the possibility to treat aggressive meningiomas with a drug already successfully used for the treatment of some leukaemias, germ cell tumours and a type of tumour of the gastrointestinal tract. The condition for this drug to be effective is that tumour cells express a molecule called stem cell factor receptor (KIT), which is known to regulate the growth of neoplastic cells. We have investigated 100 cases of meningioma and we observed that KIT is more intensely expressed in aggressive lesions but much less so in benign examples. This evidence suggests that KIT may play a role in the transformation of a benign meningothelial tumour in higher grade lesion. Using a recent, sophisticated technique called expression microarrays, we are now conducting studies in collaboration with the University of Liège, Belgium to understand if KIT is functionally active and on the molecular mechanism regulating its activity in aggressive meningiomas. If these latter experiments are successful, the next step will be to propose a medical treatment, using the existing drug, for recurrent meningiomas as an alternative to radiation therapy.