Genes may help to identify new drug targets for glioblastoma
Glioblastoma Multiforme (GBM) is one of the most common and aggressive forms of brain tumour. In addition to infiltrating into surrounding brain tissue, it also has a high potential to become malignant and the cancer cells can enter into the bloodstream and move to other parts of the body.
There is an urgent need to gain a greater understanding of GBM in order to develop better therapies that will be more effective in treating the condition. One way in which we can do this is by identifying factors that initiate the tumour and stimulate it to grow, as these can then help us to target drugs to kill the cancer cells or prevent them from spreading.
Many cancer genes have been identified, some of which have associated with inherited forms of tumours. An example is the BRCA gene which significantly increases the chances of developing breast cancer. However, the direct inheritance of GBM is extremely rare, so it is unlikely that any single gene alone is responsible. The situation is made more complex by the fact that not all people with a specific gene mutation will go on to develop a tumour but rather that genetic mutations increase the risk of developing the tumour rather than being the sole factor associated with it. A tumour will only develop if cells that are more sensitive and are then combined with additional external factors, many of which we don’t yet understand.
By examining the genes that may be altered in GBM, we will get a better understanding of what is happening within the cells when they become tumourous but also potentially identify targets at which new drugs can act.
A recently published research paper assessed the potential role of one gene that has been associated with GBM. The GRP94 gene was identified as being expressed at higher levels in glioma cells. In the current study, the researchers used a number of different approaches to bring levels back to normal and this decreased their ability to divide and spread. What is particularly interesting is that the gene is associated with a biochemical pathway within the cell that has previously associated with glioma cells called the Wnt/ß-catenin pathway. This is also controlled by a number of other genes within the cell. Some of these controlling factors may also play a role in controlling cell growth and development and may therefore play a role in cancer development. Specific biochemical pathways within the cell such as Wnt/ß-catenin may therefore provide a potential target for drugs to halt the division and spread of glioma cells.
This study highlights how a greater understanding of how specific genes work within a cell can help us to identify novel drug targets. Work is already being carried out to identify potential drugs which may act on Wnt/ß-catenin pathway. But there are many other potential targets that have been identified to play a role in cell division which may have a relevance for tumour development and for some of these, drugs may already exist. This exciting area of research is called “drug repurposing” where drugs which have been designed for one condition may be of potential use for others. This is a key are of interest for Brain Tumour Research and research funded by the charity has identified that anti-depressant drugs may have a beneficial effect for the treatment of gliomas.
While drug repurposing holds great potential for the treatment of a number of different conditions, regulatory obstacles exist to prevent this being brought forward more rapidly and Brain Tumour Research is working with a number of other agencies to ensure that these are overcome.
Dr Kieran Breen – Director of Research