Medulloblastoma is one of the most common and most malignant brain tumours among children and teenagers. These tumours grow very rapidly, and fifty percent of patients in the long term die from the condition. The details of the processes that lead to the growth of these tumours have remained unknown until now.
In two studies, working together with international scientific teams, LMU medical scientist Dr. Ulrich Schüller has now successfully revealed certain molecular mechanisms that lead to the development of these cerebellar tumours. As reported in the current issue of the journal "Cancer Cell", the researchers triggered genetic changes in cell populations in the brains of mice in order to provoke the growth of tumours. It turned out that medulloblastomas arose from only one type of cell - granule cells - and only if these were already fully committed. "Medulloblastomas are presently treated with nonspecific methods," states Schüller. "Our results could contribute to the development of targeted therapies, and thus improve the treatment of cerebellar tumours in children."
When children develop cancer, about every fifth tumour is a brain tumour - and every fifth of those in turn is a medulloblastoma. This common tumour occurs most of all in children under ten years of age, but also occurs in adults, albeit very infrequently. Up to now, medulloblastomas have only been treatable with the standard tools of cancer medicine: operation, radiotherapy and chemotherapy. Surgical interventions to treat this condition, like all operations on the brain, are particularly delicate, since it is difficult to remove the tumour completely without affecting healthy tissue. Because these cerebellar tumours scatter easily throughout the brain and even in the medullary canal, many cases result in metastases, that is the growth of secondary tumours, and not infrequently to a relapse of the original tumour - often even after successful conclusion of the treatment.
That is why patients and doctors are hoping for more targeted therapies that promise better therapeutic outcomes. "But for that to be possible, we first need to understand the principles of how the tumours develop," says Schüller. "If we know how a tumour arises at the molecular level, we can also develop specific therapies that actually treat the cause of that particular condition." Since it was still unknown from what type of cell and at what stage of development medulloblastomas arise, the researchers induced specific genetic changes in various cell populations in the brains of mice. This "conditional knock-out" method provoked changes in the so-called sonic hedgehog signalling pathway. Various processes in the development of nerve cells are controlled by this molecular signalling cascade. "Normally, the signalling pathway ensures a balance of growth and maturation of cells," says Schüller. "But if disrupted, it can lead to uncontrolled growth of cells - and thus the onset of cancer".