At the heart of Ewing sarcoma lies a unique genetic abnormality caused by a fusion between genes, which creates a faulty protein called EF1.
EF1 acts like a faulty switch in the cell, turning on genes that would normally stay silent and promoting the uncontrolled growth of cancer cells.
Researchers have discovered that cancer cells, including those from Ewing sarcoma, release small particles called extracellular vesicles (EVs). These are tiny bubble-like structures and can be taken up by other cells in the body, potentially allowing cancer cells to "communicate" with and influence surrounding cells, including immune cells and other normal tissues.
In other cancers, such EVs have been shown to play a role in helping tumours avoid immune attack and spread to other parts of the body.
EF1 has been found in these EVs in Ewing sarcoma cells. However, it remains largely unknown which exact functions EF1 carries out inside healthy immune cells or other cells within tumours.
The research group aims to determine whether the faulty EF1 protein and its genetic material can be transferred from Ewing sarcoma cells to other cells via EVs, and whether this transfer contributes to disease progression. The study will also examine if the presence of EF1 alters the behaviour of surrounding immune or healthy cells, potentially causing the cancer to spread and/or enable immune evasion.
This research may also help to uncover new ways to disrupt cancer growth by targeting these interactions as well as seeing if transferred EF1 impairs the immune response. Potential next steps might be to develop drugs that block EF1 release or uptake, improving patients’ responses to existing treatments like immunotherapy.
This research has been awarded to Dr. Maximillian Knott at the German Cancer Research Center.