OUR RESEARCH PROGRAMME

The Edward Showler Foundation Clear Cell Sarcoma Research Programme at UCL.

The money we are raising is funding the Edward Showler Foundation Clear Cell Sarcoma Research Programme at the Cancer Institute at University College London (UCL).

The funds provided have supported this programme and have also been a catalyst for other charities to invest directly into the programme through UCL; Sarcoma UK, The Jean Shanks Foundation, Transcend Sarcoma and others, which would not have happened without the Foundation having invested first.

The Foundation also received a gift of €100,000 from a private donor. This has been used to fund a laboratory technician to collect Clear Cell Sarcoma tissue samples of the gastrointestinal tract (GI). This has extended the scope of the programme and will increase our understanding of Clear Cell Sarcoma of the GI and differentiate this type of Clear Cell Sarcoma from Clear Cell Sarcoma of the soft tissue. This will lead to a better understanding and possibly treatments that specifically target this variant of the disease.

Our Scientific Team

Most of the initial aims have been achieved thanks to the dedicated work of Professor Nischalan Pillay and his team at the Sarcoma Genomics Lab at UCL - Christie, Akanksha, Leo, Tom and Sidi and others. We would like to warmly congratulate Nischalan, who was made a Professor of Cellular Pathology at UCL in the summer o.

Research Focus

As clear cell sarcoma is a very rare disease there has been little ongoing research focused exclusively on this disease until recently. When we started this journey there had been little research into the causes and drivers of Clear Cell Sarcoma and the principal aim of the research programme was to better understand these processes, before moving on to the next stage of identifying targets for treatment, developing or repurposing drugs and supporting clinical trials.

Three current areas of research most pertinent to clear cell sarcoma are:

  • Testing of medicines that block certain molecules, called kinases, that drive cells to grow and divide and which are switched on by the gene rearrangement in clear cell sarcoma

  • Investigating the underlying genetic damage (mutations) present in clear cell sarcoma cells that might contribute to the initiation or progression of disease

  • Investigating whether the immune system could be exploited or boosted to recognize and attack clear cell sarcoma cells

Whilst research into other more common cancers can sometimes be relevant to clear cell sarcoma, each particular type of cancer is unique with important differences in the fundamental processes driving disease. Better understanding of these processes is essential for the identification of effective targets for treatment. By supporting research focused on clear cell sarcoma we hope to further the understanding, and ultimately improve the treatment, of this devastating and neglected disease.

Key Discoveries

The genes usually involved in Clear Cell Sarcoma are EWSR1 and ATF1, which fuse together incorrectly in what is known as a translocation. In very rare cases there are other gene fusions but EWSR1 is always involved.

The research has confirmed this mutation through genetically sequencing the large batch of Clear Cell Sarcoma tissue samples collected so far.

The ongoing analysis of these samples, using various techniques, some of which are so novel they were not available when we started the Programme, is helping to further understand the disease and what controls its growth and development.

UCL are looking at protein degraders that will destroy the EWSR1:ATF1 fusion by specifically targeting the ATF1 gene product.

EWSR1 is involved in a number of translocational sarcoma fusions and not just Clear Cell Sarcoma.

Exploring New Approaches

Professor Pillay is also keen to pursue links with other researchers at UCL, whose work may have some relevance to Clear Cell Sarcoma. An example of this is T-cell therapy. UCL is a world leader in T-cell therapy, which seeks to activate the body's own immune response to destroy cancer cells. Whether this could be adapted to effectively degrade Clear Cell Sarcoma tumour cells has yet to be explored.


INTERNATIONAL COLLABORATION

We have raised awareness of Clear Cell Sarcoma, particularly in the scientific and medical community and have helped to galvanise research being undertaken in different laboratories across Europe and the UK to be aware of each other. This of course could not have happened without the willingness of others to collaborate in order to achieve the greater good.

European Research Network

UCL have established a network of institutions who are now sharing Clear Cell Sarcoma research which include:

  • The West German Cancer Centre (Essen)

  • The German Cancer Research Centre (Heidelberg)

  • VIB-KU Center for Cancer Biology (Leuven, Belgium)

  • University of Zurich (Switzerland)

  • The Institute for Cancer Research at the Royal Marsden Hospital (London)

  • Gustave Roussy (Paris)

  • The Christie (Manchester)

  • Institute Curie (Paris)

  • Biopticka Laboratory (Czech Republic)

  • Cork University Hospital (Ireland)

  • The Medical University of Graz (France)

Clear Cell Sarcoma Working Group

A group of scientists and clinicians from UCL, the University of Duisburg-Essen and the German Cancer Research Centre in Heidelberg, formed a Clear Cell Sarcoma working group and have been collaborating on Clear Cell Sarcoma research and sharing information. We are particularly indebted to Professor Sebastian Bauer, Dr Priya Chudasama, Dr Dawid Kreciesa and Professor Nischalan Pillay for their time and commitment to this effort.

International Clear Cell Sarcoma Workshop

Arising from this collaboration was the first ever International Clear Cell Sarcoma Workshop, which was held at the Royal Society of Medicine in London on the 17th and 18th September and was jointly hosted by UCL and the Edward Showler Foundation.

The Workshop gave the chance for Clear Cell Sarcoma scientists, researchers, clinicians and patients to meet.

The first day of the Workshop was specifically for patients and patient advocates to exchange experiences and to discuss their disease with some of the top Sarcoma clinicians in Europe. It was also an opportunity to shape the direction of future research, a vital component informing the proceedings of the second day of the Workshop, which was for scientists, researchers and clinicians from the UK, Europe and the US, to discuss different approaches to future Clear Cell Sarcoma research.

Nearly 30 scientists attended and they were invited to give presentations on different aspects of Clear Cell Sarcoma, covering a range of themes from its biology, therapeutic discoveries and details of preclinical trials and translational research.

The meeting was held in an open, friendly and collaborative manner with ideas generously shared and discussed. A number of exciting new targets and approaches for further research were identified.

Research Roadmap

Following the Workshop, a Roadmap for the direction of Clear Cell Sarcoma research has been produced which will shape the future programme of work and where it will be undertaken with international collaboration being central to how this moves forward.

The Roadmap also seeks to avoid the unnecessary duplication of research, which will hopefully ensure the resources invested are used to maximum effect.

Wider Research Efforts

Some work on EWSR1 protein degraders is being funded by Cancer Research UK as part of its Cancer Grand Challenge Programme through a group called KOODAC, an international collaboration involving scientists from the UK, US and Germany together with the US pharmaceutical company, Nurix. We are watching this research with great interest and we understand they are making progress.

Further work on EWRS1 fusion cancers and specifically Clear Cell Sarcoma is being undertaken at Harvard University in the US under a team led by Professor George Demetri, that is being funded by a large international philanthropic foundation.

With UCL, we have engaged with this Foundation, with a view to them supporting ongoing research into Clear Cell Sarcoma, in conjunction with the work they are currently funding at Harvard University. We see this as being a further collaboration that will help achieve our overall goal of finding a cure for Clear Cell Sarcoma.

FNIH ULTRA Programme

A few weeks after the Workshop, the Foundation for the National Institute of Health (FNIH) in the US, announced its ULTRA Programme had selected Clear Cell Sarcoma and another sarcoma, from over 250 rare cancers, on which to focus their future research efforts.

The FNIH seeks to form public-private partnerships to accelerate biomedical research and has raised over $1.5 billion dollars since it was founded in 1990.

They selected Clear Cell Sarcoma because they considered it had a mutation that is targetable, and due to the limited number of patients affected, it is unlikely pharmaceutical companies will specifically invest to find a cure.

The FNIH is holding a meeting in Washington DC on the 22nd and 23rd January 2026, with a view to prepare a roadmap for future research. Having already produced such a plan we are very aware of the potential this represents and are in contact with the FNIH to hopefully form collaborations with institutes in the US.


CURRENT &
UPCOMING TRIALS

There is an upcoming drug trial for metastatic Clear Cell Sarcoma patients (SARC 045), which is due to start recruiting in early 2026.

The trial drug, called Kimmtrak, is being provided by Immunocore, a UK based pharmaceutical company. The trial will recruit in centres in the US and at the Royal Marsden Hospital (RMH) in London.

Kimmtrak is a T-cell immunotherapy drug specifically targeting a cell protein called gp100. The drug is currently used to treat metastatic uveal melanoma, and this receptor (gp100) is found in both Clear Cell Sarcoma and melanoma tumours, but in very few other cancers.

Kimmtrak can only bind to cancer cells in patients who have a specific genetic marker (HLA subtype HLA-A*02:01), which will be tested upon recruitment to the trial.

We are in contact with the RMH to provide assistance in recruiting patients for the trial.

Participating in the trial

If you would like to participate in the trial then please make contact with The Edwards Showler Foundation at info@edwardshowlerfoundation.com or telephone on 07740 871683 or alternatively contact Dr Andrea Napolitano at the RMH at andrea.napolitano@rmh.nhs.uk

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