Dr Nezha Benabdallah
University of Edinburgh
Awarded: £173,874
Supported in part by funds raised through the Synovial Sarcoma Fund
The challenge
Treatments for sarcoma still rely predominantly on methods like chemotherapy, radiotherapy, and surgery. These can cause serious side effects and different people have varying outcomes.
Sarcomas are often caused by abnormalities called oncofusions, which form when two genes fuse together in a way that shouldn’t happen. These oncofusions drive cancer growth. Identifying or understanding more about them could lead to new options for more specific treatments with less serious side effects.
How will this project tackle this challenge?
Some oncofusions are linked to specific sarcomas, others can appear in multiple different types of sarcoma. Recent work by the team found that, surprisingly, different sarcomas sometimes use the same process to grow and survive. This means if a treatment was found that targeted a specific oncofusion present in multiple sarcoma subtypes, it could potentially be used to treat all of them.
In this project, the team will investigate approximately 20 oncofusions found in aggressive sarcomas. Using cutting-edge lab tools, they’ll test whether these oncofusions behave in the same way as those already studied. They’ll focus on how they influence which genes are turned on or off in cancer cells.
The team will also work to identify any molecules called cofactors. These are helper molecules that support the oncofusions. If the cofactors are essential for sarcoma growth, and they are present across multiple types of sarcomas, they could be a common weak point and another potential target for treatment. The researchers will use powerful gene-editing technology (CRISPR) to remove these cofactors and see how it effects the cancer growth in cells. If removing a cofactor stops the cancer-driving fusions from working, it could lead to a brand-new treatment strategy.
What this means for people affected by sarcoma
By identifying shared weak points in different sarcomas, the researchers aim to design a single treatment that works for several sarcoma types.
In the future, the team plans to turn the discoveries into real therapies by testing potential drugs in lab models. This could open the door to clinical trials and new, targeted options for people living with these challenging cancers.
