What is glioblastoma?

Glioblastoma is the most aggressive type of primary brain tumour in adults. It arises from glial cells (the support cells of the brain) and grows quickly, infiltrating into surrounding healthy brain tissue. The classic features at diagnosis include headaches, seizures, weakness or sensory changes on one side of the body, speech difficulty, or changes in thinking and personality, depending on where the tumour is located.

Why it has been so hard to treat. Several biological features make glioblastoma difficult. The tumour cells infiltrate widely into surrounding brain tissue, so complete surgical removal is essentially impossible. The blood-brain barrier limits access of many systemic therapies. The tumour is highly heterogeneous, with different cell populations driving growth at different times. And the brain itself cannot tolerate the kind of aggressive multimodal therapy used in some other cancers without unacceptable damage.

The modern molecular picture. The newer understanding is that what used to be called by a single name actually represents several distinct molecular categories. Adult diffuse gliomas are now classified by features including IDH gene mutation status, 1p/19q chromosomal codeletion, MGMT promoter methylation, and other molecular markers. The classification matters because different categories respond differently to therapy.

The therapy options.

For IDH-mutant grade 2 glioma after surgery: vorasidenib, an oral medicine that blocks the mutant IDH protein, is now approved. This is the first targeted therapy specifically for an adult diffuse glioma category and reshapes the early-stage management of these tumours.

For glioblastoma (IDH-wildtype, grade 4): the standard approach remains maximal safe surgical resection, followed by radiation given concurrently with temozolomide chemotherapy, then maintenance temozolomide. Tumour-treating fields (a wearable device that delivers low-intensity electrical fields to the tumour area) add benefit when used during and after maintenance therapy.

For recurrent glioblastoma: options include bevacizumab (an antibody that targets blood-vessel growth), lomustine chemotherapy, re-irradiation in selected cases, and trial enrolment for emerging therapy.

The research frontier. Several approaches are in late-stage trials. Immunotherapy combinations specifically designed for the brain, CAR-T cell therapy approaches, focused-ultrasound techniques to temporarily open the blood-brain barrier so medicines can reach the tumour, and additional mechanism-targeted therapy for molecularly-defined subgroups are all in active development.

What to expect. Glioblastoma remains a serious diagnosis with substantial challenges. Modern molecular characterisation, the established Stupp protocol plus tumour-treating fields, and the growing trial landscape have improved outcomes incrementally; the next several years may see more substantial change as molecular targeting and novel delivery approaches mature.