Professor Richard Jenner
University College London
Awarded: £149,973
The challenge
Endometrial stromal sarcoma (ESS) is a rare cancer of the womb, with 30-60 new cases each year in the UK. ESS is primarily treated by surgery to remove the womb, but the disease often comes back after treatment. Sadly, outcomes can be poor because we do not understand the molecular changes that cause this cancer type.
The science
ESS arises from endometrial stromal cells, which form the womb lining. Most cases contain a genetic change that causes two different proteins to become fused together – a ‘fusion protein’. These fusion proteins are also found in other rare sarcomas. Professor Jenner and his team recently gained insight into how the most common fusion protein, JAZF1-SUZ12, causes ESS.
Normally, endometrial stromal cells change during the menstrual cycle to make the womb receptive to the embryo or, if pregnancy doesn’t occur, to promote menstruation. As part of these changes, endometrial stromal cells cause their own death by secreting molecules that induce immune cells to attack them. But, as the team discovered, JAZF1-SUZ12 prevents these changes in stromal cells through an enzyme called NuA4. This then stops the cells from behaving as they should.
The project
In this project, the team now want to research whether JAZF1-SUZ12 causes ESS by preventing immune cells from killing endometrial stromal cells. They will also determine whether the fusion proteins found in high-grade ESS have the same effect, or whether they do other things to cells that explain why they cause more severe disease. Finally, they will test whether drugs that inhibit the enzyme, NuA4, can prevent the damaging effects of fusion proteins.
What this means for people affected by sarcoma
The experiments will be performed in a lab using endometrial samples kindly donated by healthy women and by ESS patients as part of their normal treatment. The team hope that this research will lead to new treatments directly targeting the effects of ESS fusion proteins being tested in patients within 10 years.
We need to better understand the biology of endometrial stromal sarcoma in order to develop new treatments and so we are excited to be undertaking this new research project. We hope that this project will lay the groundwork for new targeted treatments for this cancer.
