The Science Behind Glioblastoma

CN: picture of brain surgery

​How do brain tumours form?
A brain tumour occurs when brain cells divide and grow in an abnormal and uncontrolled way. When a cell divides, it copies its genes and replicates itself. Sometimes however, mistakes occur in this process, and are known as mutations. Whilst some mutations are harmless, others cause the cell to divide uncontrollably.
 
The mutation causes the cells to behave as though they are receiving a growth signal or deactivates the checkpoints that would stop the cells from dividing. Therefore, the cells continue to divide uncontrollably, forming a tumour

​What is glioblastoma?
 
Glioblastomas are the most common and aggressive type of brain cancer that forms from cells called astrocytes in the nervous system. They belong to a group of brain tumours called gliomas, which are malignant tumours of the glial tissue. The average age of patients with glioblastoma is 64 years old; its risk increases with age. Whilst glioblastomas are mostly found in the cerebral hemispheres, they can be found anywhere in the brain.
Glioblastoma is a ‘diffuse’ tumour, meaning they are infiltrate and able to spread into healthy tissue in other parts of the brain, and therefore is very fast growing and fast spreading. This makes it very difficult to pinpoint precisely where the tumour starts and ends. Particularly aggressive glioblastoma are able to even spread to the opposite side of the brain through connection fibres, known as corpus callosum. Gliobastoma’s ‘diffuse’ property is particularly problematic when tumours spread near to important regions of the brain that are essential to functions such as movement and coordination.

​Symptoms and side effects of glioblastoma
Due to mass swelling from the fluid surrounding the glioblastoma (edema), patients develop symptoms very quickly. The most common symptoms are nausea, vomiting and severe headaches, and are predominantly due to the increased pressure in the brain as a result of the tumour and swelling. Neurological symptoms are also not uncommon, for example, weakness, sensory changes, difficulties with balance, and neurocognitive or memory issues.
 
Treatment of glioblastoma
Mark Gilbert, director of the Neuro-Oncology Branch in NCI’S Centre for Cancer Research said, “Glioblastoma is one of the hardest to treat in the history of oncology.” Despite continued efforts to develop promising treatments for glioblastoma, none have proved successful, with only 3.3% of patients living for longer than 2 years. The usual treatment for patients with glioblastoma is a surgery to remove most of the tumour, followed by chemotherapy and radiation.

​Surgery
Commonly, surgery would take place in an attempt to remove as much of the tumour as possible- a procedure known as debulking. It is difficult to remove the entire tumour because glioblastoma is a diffuse tumour, which means it can spread into the rest of the unaffected brain, and so it is difficult to tell the difference between affected and unaffected brain tissue.
There have been recent advances, which have improved the extent to which the tumours  can be removed in surgery. Prior to surgery, patients are given a drink containing the substance 5-ALA, which causes the affected cells to glow pink under violet light. This makes it less difficult to tell the affected and unaffected cells apart, and so more of the tumour can be removed.
Surgery is also used for palliative treatment in cases where the tumour cannot be removed- intracranial pressure is reduced to relieve symptoms.
 
Radiation
Radiation involves the use of high precision high-energy beams, for example X-rays, gamma rays or protons, to kill the affected cancer cells.  An immobilization mask is worn by the patient to hold their head in the same position and limit movement. Intensity-modulated radiation therapy is an advanced mode of radiotherapy that uses computer-controlled liner accelerators to deliver precise radiation doses to a malignant tumour. It allows for the radiation dose to conform more precisely to the 3D shape of the tumour by controlling the intensity of the beam in small volumes. The treatment is planned specific to the tumour using the CT and MRI images of the tumour in conjunction with computerized dose calculations to determine the dose intensity pattern that is best suited for the tumour.

​Chemotherapy
Chemotherapy is a technique that uses cytotoxic drugs to kill the affected cancer cells. Temozolomide, Iomustine and carmustine are the most commonly used drugs in chemotherapy. Temozolomide works by preventing the tumour cells from making new DNA, which prevents them from making new cells and therefore growing. It also makes the affected cells more sensitive to radiation, so chemotherapy and radiation treatments are often used together. Whilst radiation acts on the affected tumour cells, chemotherapy acts on all dividing cells, but healthy cells are able to repair themselves easier than the tumour cells, so few healthy cells die after treatment. The various ways in which chemotherapy can be given are:
 
Tablets- chemotherapy drugs can be taken in tablet form and are absorbed and carried around the body in the bloodstream to reach the affected tumour cells.
Injection/drip- chemotherapy drugs can be injected into a vein or into the spinal fluid. A drip may be used to insert the drug into the bloodstream, where it is absorbed and carried around the body to the affected cells.
Wafers- drugs can be put inside a polymer wafer and inserted into the brain during surgery. The wafers are made of a biodegradable material so they can dissolve over a few weeks, releasing the drug into the brain to kill the tumour cells.
 
Immunotherapy-Vaccinations
Whilst several immunotherapy-based treatments have proved unsuccessful in facing glioblastoma, vaccinations has been considered to be one of the more promising approaches.
A particular advance in the use of vaccines for glioblastoma was made by Dr Jason Adhikaree from the University of Nottingham, who proposes to use dendritic cells, a type of white blood cell, to create the vaccine. The dendritic cells would be taken from the patient’s body and ‘taught’ to recognise and kill the glioblastoma-affected cells. They will then be injected back into the patient’s body, in which they can attack the tumour cells.

By Maheria Rashid