Playing Chess with Glioblastoma

We hear about precision therapy for glioblastoma, that is, the possibility of analyzing the genes of the specific tumor person and of using specific therapies to treat that specific tumor, maximizing efficacy. These types of therapies differ from protocols that must conform to all glioblastoma patients, such as the famous STUPP protocol.

In these days a very interesting work has been published describing a case of application of a personalized and precision therapy: Impressive response to dabrafenib and trametinib plus silybin in a patient with wild-type IDH glioblastoma heavily pretreated with BRAFV600E mutant and SOX2 amplification. I liked the work even if it refers to a single case because it tells a kind of chess game between doctors and the patient on one side and glioblastoma on the other. This helps to understand and how these therapies work and how effective can be.

Wild-type glioblastoma is the most frequent primary brain tumor in adult patients and its prognosis is still poor with a median survival of approximately 1 year. The BRAFV600E mutation, an important target for personalized therapy, was identified in approximately 3% of these patients. These patients can be given BRAF inhibition. However, glioblastoma sometimes responds with expression of the SOX2 gene which may represent an important mechanism of resistance to BRAF inhibitors by activation of gene STAT3.

The case study examined by the article refers to a 42-year-old man with heavily pretreated glioblastoma (i.e. a patient who has already done several treatments which however proved to be ineffective) with BRAFV600E mutation and SOX2 amplification. The patient, treated at the Istituto Oncologico Veneto of Padua, had a complete response to dabrafenib plus trametinib and silybin, a powerful inhibitor of STAT3. The patient is currently still on treatment after a total of 24 months with maintenance therapy.

To glioblastoma that over-expressed the SOX2 gene, doctors responded by adding silybilin to the treatment which inhibits the STAT3 gene, which in turn resists BRAF inhibitors.

The result is promising and demonstrates how personalized treatment with BRAF inhibitors in patients with glioblastoma with the BRAFV600E mutation and silybin play an important role in reducing drug resistance during BRAF inhibitor therapy.

In short, a kind of chess game with moves and counter moves. These personalized and precision therapies can be a solution at least for patients with mutations for whom there is an effective drug or drug combination. Certainly these therapies are not easy to apply: the patient must go to a specialised center where it is possible to carry out a complete genetics analysis of the glioblastoma and an entire team must think about the specific case but in this way what seems impossible becomes possible.

I hope I have told you in the simplest way possible how precision therapy works by examining a documented case. It is to be hoped that more and more effective precision therapies will become available and more patients may have a hope of long-term survival.