Dr Nischalan Pillay
University College London
Awarded: £119,479
What are clear cell sarcomas?
Clear cell sarcoma is an ultra-rare soft tissue sarcoma that mostly affects young adults. It can occur anywhere, but it is most commonly seen in the tendons of the feet. Clear cell sarcoma doesn’t respond well to chemotherapy or radiotherapy, and can spread to the lymph nodes and the lungs. This sadly means patient outcomes are often poor.
Why is understanding the biology of clear cell sarcoma important?
Clear cell sarcoma is caused by a specific type of mistake in the DNA, where one gene called EWSR1 is joined, or fused, to another called ATF1. The resulting ‘fusion protein’ causes the cells to become cancerous. Studying the cells of clear cell sarcoma can help us understand it better and show us how to treat it. More than 100 samples of clear cell sarcoma have been collected and stored in biobanks for many years. 50 of these are frozen, which means their DNA has been preserved to a very high quality. This makes them an incredible resource for a cancer this rare.
What have this team done previously in clear cell sarcoma?
The team have joined up with the Edward Showler Foundation, a charity whose mission is dedicated to clear cell sarcoma research. Under a huge programme of research funded by the Foundation, the team are analysing these samples to uncover the mechanisms that cause clear cell sarcoma to develop and grow. The team behind the project are world-leaders in their fields and they will also provide training for a PhD student to take their first step into sarcoma research.
How will this project tackle this challenge?
In this project, the team will use cutting edge cell sequencing technology, working with scientists from the University of Oxford. They aim to understand how clear cell sarcoma cells differ from those around them and identify subpopulations of cells that could be targeted by drugs.
They will then use this data to undertake pioneering pre-clinical drug discovery work to design a new and exciting class of drugs called PROTACs. PROTACS can degrade fusion proteins, like those seen in clear cell sarcoma, in other cancers. They can also specifically target tumour cells and show less toxic side effects.
What this means for people affected by sarcoma
This is a hugely exciting project, aiming to answer vital unanswered questions about clear cell sarcoma. It could also bring us closer to better treatments, and may provide evidence for early-stage clinical trials. If successful, the science behind the project could be applied to sarcomas with similar biology, such as synovial sarcoma or Ewing sarcoma.
