Dr Cribbs and Dr Cottone explain more about the aims of the new chordoma research project and what difference their research could make for future patients.
Can you tell us about the project and its aims?
Chordoma is a rare slow growing bone cancer that can occur in the vertebral bones from the base of the skull to the coccyx. Given its close proximity to the spinal cord, chordoma is difficult to treat, and very few drugs are available for inoperable and metastatic disease.
Our research aims to identify novel epigenetic pathways that regulate chordoma development and that can be targeted using specific drugs.
Epigenetics is the addition of information on top of the DNA sequence of letters (strings of molecules called nucleotides - A, G, C, T). This is achieved by adding a variety of chemical modifications, called marks, to the nucleotides and different epigenetic marks control the expression of different genes.
We have recently shown that a subset of such epigenetic marks controls the expression of brachyury, a gene critically involved in the development of chordoma, and that blocking these epigenetic mechanisms effectively leads to chordoma cell death in laboratory studies.
In this project, using computer softwares, we will generate an ‘epigenetic map’ of disease which will highlight the processes contributing to this disease in more detail. Using this map we will be able to identify regions of DNA that are involved in chordoma development and that can be used to identify novel therapeutic targets for this bone tumour.
Overall, the goal of this project is to generate a shortlist of epigenetic targets that can be used to advance drug development for chordoma.
What difference could this project make for Chordoma patients in the future?
The development of new medicines is required to improve patient outcomes and their quality of life. Unfortunately, despite recent advances and the identification of novel therapeutics like EGFR inhibitors, there is a severe lack of targeted therapies to treat chordoma. The goal of this project is to identify novel epigenetic inhibitors that can switch off brachyury, that are effective in controlling chordoma growth in the laboratory, and that could potentially be a future drug for the treatment of chordoma. Importantly, we will share our results with the chordoma community and the wider scientific community, and this will help increase our knowledge on the causes of this rare cancer.
Can you tell us more about the collaboration between the University of Oxford and University College London?
Collaboration is key to scientific discovery and our work on chordoma is no exception. The reason for the collaboration between Oxford and UCL is to facilitate expertise, knowledge and reagent transfer.
The UCL team have pioneered research into the role of brachyry (a gene important for driving chordoma) and the genomic landscape of chordoma, and will contribute knowledge and expertise in understanding chordoma biology. However, the Oxford team have a different set of skills, which include chemical biology and computational tool development. Using our overlapping and distinct skill sets we will apply these to identifying drugs that can be used to treat chordoma in addition to understanding the mechanisms of disease.
How important is the funding provided by the Bone Cancer Research Trust and what would you say to our supporters who are raising funds for research?
Without the support of the Bone Cancer Research Trust, this research would simply not be possible. Most large cancer charities typically shy away from rare bone cancers because the funding justification can be difficult when compared to common cancers. This is where the Bone Cancer Research Trust, with its specific remit of only funding research in bone cancer, helps to deliver life changing research that is not currently fulfilled by larger and more broad cancer charities. Bone cancers can be horrific not only for patients, but also for their families, friends and work colleagues. We believe that there are potential treatments and cures for chordoma, but the only thing preventing their realisation is adequate funding for research. We would like to thank all of those people who have donated to the Bone Cancer Research Trust in the past and would like to encourage those that are yet to support the charity. Without their generous donations and support this work would not be possible.