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Glioblastoma (GBM) is the most common and most aggressive form of adult brain cancer. Patients who receive surgery, radiation therapy and chemotherapy only have insufficient life-expectancy. This is as a result of the re-growth of the tumour in most patients after surgery, with this new tumour now resistant to treatment.
It is vital that new treatment for GBM tumours be developed in order to address the poor outcome for GBM patients. Annually 250,000 - 300,000 patients globally are diagnosed with brain and nervous system tumours, of which GBM is the most common and there is no definitive cure available currently. Despite advances in care, patient outcomes are still poor. Two of the main causes of treatment failure are the invasion of tumour cells into the surrounding brain tissue, and the extreme resistance of tumour cells to radiation and chemotherapy. The invasive nature of this type of tumour makes complete surgical removal impossible, leading to recurrence of tumour growth. Thus, it is imperative that any new treatment strategy addresses the invasive nature of the tumour. However at present there are no anti-invasion therapies available for use in the clinic for GBM patients.
- Occurs more commonly in men
- Occurs more commonly in those over 50 years of age
- GBM is more common in caucasians, hispanics and asians
- Diagnosis is made through MRI, CT and tumour biopsy
- Classified as a Grade IV astrocytoma
- Typical symptoms include: Nausea, vomiting, seizures, memory loss, hemiparesis & neurological decline.
- The tumours are generally are quite large before any symptoms are detected
- Cells can migrate far from the tumour bulk and rapidly divide
- The "blood-brain-barrier", which usually protects the brain from chemicals, creates a barrier to normal treatment options.
- The genetic heterogeneity makes these tumours extremely difficult to treat.
- There are 4 "subtypes" of GBM which are Classical, Proneural, Neural and Mesenchymal.
GBM Treatment Options
- Total resection (removal) is the best surgical option.
- There are only 3 medical therapies approved for use: Temozolomide (TMZ), Carmustine wafers, Bevacizumab
The Stupp protocol is the standard of care for patients diagnosed with GBM
GBM is not a surgically curative disease (Curative resection is difficult due to the invasiveness of these cancers) and so maximal safe surgical resection is carried out (70%) followed by concomitant radiotherapy (RT) + TMZ, and adjuvant treatment with TMZ.
Temozolomide is more efficient in "MGMT methylated" patients (~50% of patients fall into this category) and in these patients it is 100% bioavailable when taken orally and, because of its small size and lipophilic properties, it is able to cross the blood-brain barrier. Other treatments include Gliadel wafers and Tumour treating fields (TTF).
The aim of the GLIOTRAIN programme is to identify and interrogate novel therapeutic strategies for application in GBM, thereby improving patient care and survival. This will be done implementing state of the art next generation sequencing (NGS) and 'omics technologies.