What Is Glioblastoma?

Glioblastoma, or glioblastoma multiforme, is an aggressive form of brain tumour which can spread rapidly to surrounding brain tissue. 

Whilst this form of cancer is rare, it accounts for 49% of all malignant brain tumors.1 This type of brain tumour is life-threatening and currently has no cure, however, receiving treatment as quickly as possible is crucial for a better prognosis.

So, what is glioblastoma? 

  • Glioblastoma multiforme is a grade IV tumour found within the brain or spinal cord. 
  • Glioblastoma affects around 45.2% of all patients diagnosed with a primary brain tumour2 
  • Glioblastoma can quickly grow and spread to other areas of brain tissue, making it harder to treat and more likely to cause relapse post-treatment

In this article we discuss in depth what glioblastoma multiforme is, how it is caused, and the various treatment options available including those in current research and clinical trials. 


What is glioblastoma? 

Glioblastoma, or glioblastoma multiforme (multiforme meaning lots of different forms), is an aggressive grade IV malignant cancer belonging to a group of brain tumours known as gliomas. These cancers affects nerve cells known as glia which are responsible for providing structural support alongside metabolic support, nerve protection, and replacement of damaged or dead cells. The cancer causes the cells to proliferate very rapidly and spread within the brain tissue or spinal cord. Studies have shown that an untreated glioblastoma can grow at a rate of 1.4% per day and can double in volume by 49.6 days.

Depending on the type of glia cell the cancer started in and the type of genetic mutation, there are three types of glioblastoma multiforme:

Primary or secondary tumour?

Glioblastoma can either be a primary tumour or a secondary tumour. Primary, or de novo, glioblastoma originates in the brain or spinal cord. This is the most common form of brain tumor, occurring in around 45.2% of all adult patients diagnosed with a brain tumour.3 Primary glioblastoma multiforme can affect people of any age but occur mainly in patients over the age of 65. 

Glioblastoma can also develop as a secondary tumour. In the cases of secondary glioblastoma, a lower-grade astrocytoma or oligodendrocytoma has developed into a grade IV glioblastoma. Secondary glioblastoma is rare, affecting around 10% of patients diagnosed with this type of cancer. Secondary glioblastoma usually affects those ages ~45 years.4

Why does glioblastoma have a poor prognosis?

Glioblastomas have a diffuse morphology, meaning that the tumour does not havea defined border andis not well contained. The glioblastoma can form thin tendril-like projections and so the cells can easily penetrate and invade different regions of the brain and spread to surrounding healthy brain tissue. Research has also shown that glioblastoma is also able to stimulate the formation of new blood vessels (angiogenesis), which further promotes tumour progression and growth.5,6 Due to this diffuse and fast-growing nature, treatment of this type of cancer is very difficult to treat and has an increased likelihood to return.

Because this form of cancer has a very aggressive nature, the long-term prognosis of survival is usually poor. Life expectancy after diagnosis depends on a multitude of factors including where the tumour is, how much it has spread at the time of diagnosis, and how quickly a patient receives treatment. 

According to the American Brain Tumor Association, 5-year survival rates for age groups are; 

  • Children aged 0-14: 19.4%
  • Adolescents and young adults ages 15-39: 26%
  • Adults ages 40+: 5.6%

Causes of glioblastoma

Like other forms of brain tumours and brain cancers, glioblastoma occurs when genes become mutated. This causes tumour cells to grow uncontrollably and spread rapidly throughout the surrounding tissue. 

The cause of these mutations is still yet to be understood. Therefore, glioblastomas are generally thought to occur spontaneously as a result of random gene mutations occurring in nerve cells.

The most commonly observed genetic mutations occurring in glioblastoma multiforme include: 

  • De novo mutation (no clinical or histological evidence or precursor lesions). This affects around >90% of cases
  • Isocitrate dehydrogenase 1 (IDH) wildtype. This accounts for around 73% of secondary glioblastoma cases and 3 to 5% of primary glioblastoma7
  • Neurofibromatosis type 1 (NF1). Mutation of NF1 in glioblastoma is rare but has been presented in some cases8
  • Methylguanine DNA Methyltransferase (MGMT). This accounts for around 35-45% of grade III and grade IV gliomas9,10
  • Epidermal growth factor receptor (EGFR) amplification. Genetic mutation of EGFR is noted in around 20-40% of patients10
  • p16INK4A. This mutation and/ or deletion occurs within the p16INK4A tumor suppressor gene and occurs in around 31% of glioblastoma cases
  • TP53 somatic mutation (secondary glioblastoma) is present in around 60% of low-grade precursor astrocytomas11

Increased genetic risk 

Increased risk of glioblastoma development has been identified in >1% of patients with genetic diseases including neurofibromatosis 1 and 2, Li-Fraumeni syndrome, Turcot syndrome, tuberous sclerosis, or retinoblastoma.

Exposure to ionising radiation 

Ionising radiation is speculated to have an involvement in glioblastoma development. This includes repeated exposure to X-rays, such as therapeutic ratio treatments and CT scans to the head and neck area. There is also a greater incidence for those exposed to ionising radiation from a younger age vs older age.12,13

Environmental exposure

Research involving gene-environment interactions in case studies of individuals with prolonged exposure to plastics, pesticides, and solvents has shown an increased risk for glioma development.14 These include chemicals and carcinogens such as;  

  • Vinyl chloride 
  • Smoking
  • Pesticides
  • Synthetic rubber manufacture
  • Petroleum refinement 

Signs and symptoms of glioblastoma

Glioblastoma symptoms may vary depending on the location of the tumour within the brain. 

General symptoms of glioblastoma multiforme can include; 

  • Headaches, particularly those associated with raised intracranial pressure. These headaches may become worse when lying down or when triggered by Valsalva maneuver
  • Confusion and cognitive impairment 
  • Seizures
  • Memory loss 
  • Nausea and vomiting, particularly those associated with headaches
  • Changes in personality
  • Difficulties with speech
  • Vision problems (blurred or double vision) 

Management and treatment for glioblastoma

Due to the complexity and nature of glioblastoma, this tumour type can be hard to treat. However, there are options that can be explored depending on the size and location of the tumour. Treatment usually involves; 


Neurological surgery (or brain surgery) aims to remove as much of the tumour cells as possible, however, due to the morphology and rate at which it spreads, surgical removal of glioblastoma multiforme is typically unsuccessful at removing all of the mutant cells. Due to this, surgery is often used alongside other forms of treatment. 


Standard radiotherapy and gamma knife radiotherapy can be used to target and destroy cancer cells by using X-rays and protons targeted directly at the tumour. Radiotherapy is typically offered alongside surgery and other forms of treatment.

Chemotherapy (such as temozolomide)

Chemotherapy uses medication to destroy cancer cells. This can be done orally or can be offered in other forms of local delivery such as convection-enhanced delivery, implanted or injected delivery, or intra-arterial delivery. 

Salvage chemotherapy 

This is a form of chemotherapy used if the cancer has not responded to previous chemotherapy attempts. This type of treatment is more aggressive and can have various side effects. Studies have shown a positive prognosis for those with glioblastoma who received salvage treatment in benefiting survival.15

Other drug therapies (Bevacizumab and Lomustine)

Targeted therapy aims to use medication that is specially made to block chemical messages by the tumor cells to destroy them. 

Supportive therapy 

These are utilised to combat side effects and tumor-related symptoms. This includes using medications such as antiepileptics or corticosteroids. Side effects of treatment can include peritumoral edema (accumulation of water around the brain), venous thromboembolism (blood clot in veins), seizures, and cognitive dysfunction. 

Targeted therapy 

Targeted therapy is a type of therapy which aims to interact with specific genes and proteins that aim to reduce tumour growth and progression. This form of treatment includes; 

  • Immunotherapy involves using a patient's immune system to disrupt cancer cell activity
  • Gene therapy aims to disable specific gene functions to stop the further spread of cancer cells.
  • Oncolytic viral therapy uses genetically modified viruses to infect and kill cancer cells. This therapy has yielded beneficial results and has been used in past clinical trials but is not yet available outside of clinical trials16

Other Future locoregional therapy in research 

New, less invasive treatments are currently being explored. This includes treatments which aim to help transport medication through the blood-brain barrier. As only 20% of systemically administered medication penetrates the brain tissue, research is currently exploring the use of thermogels and spray-dried polycaprolactone (PCL) microparticles in animal trials, with hopes to progress to clinical trials in the future. Such methods have shown promising results in increasing drug delivery in animal models.17

Palliative care 

Palliative care aims to provide comfort for the patient, utilising pain relief medication and dedicated support for patients and families. This is utilised alongside other medical treatments. 


How is glioblastoma diagnosed?

Neurological exams

Typically, a medical professional will assess the patient's symptoms and previous medical history. Tests may include observing the patient's reflexes, balance, coordination, vision/hearing, and short-term memory recall. 

Imaging tests

Brain scans aim to locate the tumour and will also allow a doctor to be able to assess the size and location of the tumour, and whether it has spread to surrounding tissues. This can come in the form of;


Removal of some of the suspected cancer cells is required to ultimately confirm the presence of glioblastoma cells. Depending on the location of the tumour, this can be done during brain surgery by removing a piece of the tissue for further histopathological analysis. 

Can glioblastoma be prevented?

No, glioblastoma can not be prevented. Due to spontaneous genetic mutation, there are no known methods that can prevent this tumour from forming. However, avoiding some potential risk factors could be beneficial in avoiding tumour development. 

Who is at risk of glioblastoma?

According to the National Cancer Institute, there are very few risk factors associated with glioblastoma. Some risk factors may include;

  • Those aged 40 or over
  • Males are more likely to receive a glioblastoma diagnosis compared to females
  • Genetic diseases may increase risk, such as neurofibromatosis 1 and 2, Li-Fraumeni syndrome, Turcot syndrome, tuberous sclerosis, or retinoblastoma (less than 1%)
  • Those exposed to ionising radiation from a young age
  • Those who have repeated exposure to carcinogens or pesticides
  • There are positive correlations to those with allergies (such as hay fever and seasonal allergies) presenting a protective effect. This may be due to a heightened immune system that may counteract tumour growth18 

How common is glioblastoma

In general, brain tumours are relatively rare compared to other forms of tumours. According to the American Cancer Society, the chance of developing brain cancer during their lifetime is less than 1%.

Gliomas are the most common form of brain tumour, specifically astrocytoma. When compared to all types of brain tumours, astrocytoma accounts for around 45.2% of brain and spinal cord tumours.3 According to Cancer Research UK, around 80 out of 100 cases with an astrocytoma are categorised grade IV glioblastoma. 

When should I see a doctor?

Whilst brain tumour diagnoses are rare, the development of new neurological symptoms must be checked by a medical professional.

Depending on the symptoms experienced, glioblastoma can be mistaken for lesser medical ailments. If you experience new neurological symptoms such as migraines, or more serious medical events such as stroke you should seek medical advice as soon as possible. ue to the growth rates and infiltrative nature of the primary tumour, treatment is highly necessary for bettering a long-term prognosis and increasing survival chances.


  • Glioblastoma is the most aggressive form of brain tumour and is generally deemed to be a terminal disease
  • Glioblastoma, whilst being the most common form of brain tumour, is still a rare form of cancer
  • There are a variety of new treatments which aim to benefit drug delivery and may improve survival in the future


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  2. Stensjøen AL, Solheim O, Kvistad KA, Håberg AK, Salvesen Ø, Berntsen EM. Growth dynamics of untreated glioblastomas in vivo. Neuro-oncology. 2015 Oct 1;17(10):1402-11.
  3. Kanderi T, Gupta V. Glioblastoma multiforme. InStatPearls [Internet] 2021 Nov 20. StatPearls Publishing. 
  4. Ladomersky E, Scholtens DM, Kocherginsky M, Hibler EA, Bartom ET, Otto-Meyer S, Zhai L, Lauing KL, Choi J, Sosman JA, Wu JD. The coincidence between increasing age, immunosuppression, and the incidence of patients with glioblastoma. Frontiers in pharmacology. 2019 Mar 27;10:200.
  5. Ahir BK, Engelhard HH, Lakka SS. Tumor development and angiogenesis in adult brain tumor: glioblastoma. Molecular neurobiology. 2020 May;57:2461-78.
  6. Das S, Marsden PA. Angiogenesis in glioblastoma. New England Journal of Medicine. 2013 Oct 17;369(16):1561-3.
  7. Han S, Liu Y, Cai SJ, Qian M, Ding J, Larion M, Gilbert MR, Yang C. IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. British journal of cancer. 2020 May 26;122(11):1580-9.
  8. Narasimhaiah D, Sridutt BS, Thomas B, Vilanilam GC. Glioblastoma in adults with neurofibromatosis type I: a report of two cases. Neuropathology. 2019 Oct;39(5):368-73.
  9. Thon N, Kreth S, Kreth FW. Personalized treatment strategies in glioblastoma: MGMT promoter methylation status. OncoTargets and therapy. 2013 Sep 27:1363-72.
  10. Montemurro N. Glioblastoma multiforme and genetic mutations: the issue is not over yet. An overview of the current literature. Journal of Neurological Surgery Part A: Central European Neurosurgery. 2020 Jan;81(01):064-70.
  11. Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. The American journal of pathology. 2007 May 1;170(5):1445-53.
  12. Braganza MZ, Kitahara CM, Berrington de González A, Inskip PD, Johnson KJ, Rajaraman P. Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review. Neuro-oncology. 
  13. Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, Wrensch MR. The epidemiology of glioma in adults: a “state of the science” review. Neuro-oncology. 2014 Jul 1;16(7):896-913.2012 Nov 1;14(11):1316-24.
  14. Rodvall Y, Ahlbom A, Spännare B, Nise G. Glioma and occupational exposure in Sweden, a case-control study. Occupational and Environmental Medicine. 1996 Aug 1;53(8):526-32
  15. Kim HR, Kim KH, Kong DS, Seol HJ, Nam DH, Lim DH, Lee JI. Outcome of salvage treatment for recurrent glioblastoma. Journal of Clinical Neuroscience. 2015 Mar 1;22(3):468-73.
  16. Zhang Q, Liu F. Advances and potential pitfalls of oncolytic viruses expressing immunomodulatory transgene therapy for malignant gliomas. Cell death & disease. 2020 Jun 25;11(6):485.
  17. Cirillo G, Spizzirri UG, Curcio M, Nicoletta FP, Iemma F. Injectable hydrogels for cancer therapy over the last decade. Pharmaceutics. 2019 Sep 19;11(9):486.
  18. Costanza M, Finocchiaro G. Allergic signs in glioma pathology: current knowledge and future perspectives. Cancers. 2019 Mar 22;11(3):404.
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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