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The Humane Research Trust is funding a research project to understand the link between specific genes and cancers like ependymoma. Researchers at Keele University are using optogenetic tools on tumour cells to investigate the role of genes in cancer development. This innovative work will help us understand the causes of brain tumours in children and advance research into new treatments.
Ependymoma is a type of cancer that affects the central nervous system. Specifically, it is found in the ventricular system of the brain and the central canal of the spinal cord. This type of tumour, although rare in adults, is the second-most common brain tumour in children. Unfortunately, the long-term prognosis remains poor and for around 40% of children, the cancer is incurable.
Currently, researchers are unsure of the exact causes of cancers such as ependymoma. Though, previous studies suggest that there is likely a genetic component. Researchers want to find out which genes are ‘switched on’ or ‘off’ in cancer cases. These ‘mistakes’ in the DNA, otherwise known as mutations, could help us understand how tumours can form.
One recently discovered mutation, commonly found in one region of the brain, involves a portion of one gene called ZFTA. ZFTA fuses to another gene, RELA, to make a ZFTA-RELA fused mutant gene. This results in the production of an abnormal protein, which scientists think is linked to cancer development. Understanding the role of this mutation may provide valuable insights into the mechanisms behind the development and progression of ependymoma.
A lot of research into cancers such as ependymoma relies on animal experimentation. These experiments often involve inducing tumours in live animals, which can be both cruel, and scientifically challenging. However, The Humane Research Trust is funding a research project into ependymoma at Keele University, which is using human alternatives. Dr George and his research group are using nerve cells from human stem cells to study live cell interactions.
“The crosstalk between neurons and ependymoma cells invading neural circuitry is challenging to replicate in animal models,” says Dr George. “Our approach offers an opportunity to assess cell to cell interaction for controlling cancer cell behaviour.”
In pursuit of greater disease understanding, Dr George and his team are modelling ependymoma cells in the lab. Then, they will use CRISPR, a genetic engineering technology, to modify the DNA in the tumour cells. The researchers use a technique called optogenetics, which is when they use a type of blue light to ‘switch’ the ZFTA-RELA fused mutant gene on and off in ependymoma cells. This stimulates the production of the abnormal protein. This allows the researchers to test the effect of the produced protein on the cancer cell. They can also investigate what other genes can influence the cancerous nature of cells.
The scientists hope to discover whether altering the activity of genes affects the behaviour of cancer cells. Researchers can use that information to find new medicines that target those gene functions. In addition, they can investigate how electrical activity between cancer and non-cancer nerve cells can influence cancer growth, which has not been possible using conventional animal models of ependymoma. The Humane Research Trust is proud to support this innovative research. We hope the project can shed light on the genetic aspect of disease severity.
