What is Ependymoma?

What is ependymoma?

Every family who has been affected by a paediatric brain tumor faces a challenge that few of us can imagine. But we all can understand the statistics. Although considered rare, this complex range of diseases are responsible for more mortality in our children than any other type of cancer and more years of life are lost to brain cancer than any other cancer type. There are a number of reasons why this is the case. First, treating cancer anywhere in the body is a challenge, and in the developing and growing child’s brain, it is a formidable challenge to kill tumor cells and leave the remaining brain unaffected – also, the brain is protected against toxins (including most chemotherapy drugs) by a specialized barrier that prevents the entry of many molecules. The other anchor of cancer therapy (irradiation) may kill tumor cells, but it is challenging not to damage the normal tissue surrounding the tumor. Second, until very recently, our understanding of these tumors was lacking; uncoordinated research and small numbers of archived tissues prevented genetic analysis of the mutations in these tumors – thankfully this is now remedied, and we have a better understanding of the biological mechanisms involved, and potential ways to target, many pediatric cancers. Third, research into this type of cancer is notoriously underfunded, and it is left to Charities and specialized research labs to make up for this shortfall. This is where the work of Sara Wilson and her team at Fighting Ependymoma becomes so cirtical. By raising awareness (and funds) Fighting Ependymoma is enabling the public to understand the challenge of this form of cancer, and helping to provide vital funds for scientists.

So what is ependymoma? It is a form of cancer that arises from specific cells in the central nervous system. Ependymomas are diverse and can arise at any age, and at different locations in the brain and along the spine. The majority are seen in children, and ependymomas are the third most common pediatric brain cancer (1). Because these cells grow inside of the brain they can affect normal bodily functions – with diverse symptoms, depending on tumor location and size. Ependymomas are unusually resistant to chemotherapy – therefore treatment is usually surgical, and may also employ radiation to kill remaining tumor cells. Around half of paediatric ependymoma patients will not survive beyond 5 years of their diagnosis. New treatments are clearly necessary to manage this disease. We do not know the causes of ependymoma, but biologically we do know that this disease occurs due to mutations in cells related to ependymal cells in the brain that line the fluid filled ventricles in the middle of the brain and along the spinal cord. We also know that using molecular data it is possible to subclassify ependymomas into several distinct groups (2). This information is critical as it will allow the development of therapies that target the distinct molecular biology of each of these groups (3).

All cancers are driven by mutations accumulated in an individual cell, that can be inherited or occur at random throughout our lives. Different tumor types are driven by different mutations and it is only very recently that driver mutations have been identified in ependymoma. For example it is now known that many ependymomas are characterized by a specific fusion of two distinct genes in our DNA called C11orf95 and RELA – the consequence of this fusion is that a protein in the cell (called NF kappa B) which drives cell growth is activated (4). This knowledge opens the door to new potential therapies that will target this biological pathway. There are a number of ongoing clinical trials for ependymoma, and I would expect that over the next few years with our increased knowledge of the biology of these tumors that these trials will become much more focused on specific tumor features – this gives us a much better chance to develop effective approaches. As breakthroughs are made in other tumor types that we see on the news every day it is vital that we keep accumulating knowledge on these more challenging and less common tumor types, and develop methods to overcome the many challenges they present.

I give my best wishes and full support to the efforts of Sara and her team at Fighting Ependymoma, in their quest to raise awareness and find a cure for this most difficult of cancers.
Dr Lawler.

1. Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. NeuroOncology. 2016 Mar 28. [Epub ahead of print]

2. Pajtler KW, Witt H, Sill M, et al. Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell. 2015;27:728-43.

3. Gajjar A, Pfister SM, Taylor MD, Gilbertson RJ. Molecular insights into pediatric brain tumors have the potential to transform therapy. Clin Cancer Res. 2014;20:5630-40

4. Parker M, Mohankumar KM, Punchihewa C, et al. C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma.
Nature. 2014 ;506:451-5.