The award, funded through the MRC’s New Investigator Research Grant in Molecular and Cellular Medicine scheme, will support Dr Moon’s project, “Reprogramming the Lipid Landscape to Exploit a Therapeutic Vulnerability in Metastatic Breast Cancer.”
The research aims to uncover how aggressive breast cancer cells rewire the way they process fats – or lipids – to help them spread throughout the body, and how this process could be exploited to destroy metastatic tumours.
Metastasis – the spread of cancer from the original tumour to other organs – is the leading cause of cancer-related deaths. In breast cancer, tumour cells can remain dormant for years after initial treatment before re-emerging in vital organs such as the lungs, liver or brain.
“Our goal is to understand the fundamental biology that allows cancer cells to survive during metastasis,” said Dr Moon. “If we can identify the mechanisms that cancer cells rely on to spread, we can begin to turn those same mechanisms against them.”
At the centre of the team’s research is a protein called MAFF, which acts as a molecular “master switch” controlling how cancer cells manage and remodel fats within the cell.
The researchers discovered that in highly aggressive breast cancers, MAFF dramatically rewires the cell’s lipid landscape. This transformation changes the composition of the cell membrane, making it more flexible and helping tumour cells detach, travel through the bloodstream, and establish new tumours elsewhere in the body.
However, the same adaptation that enables cancer cells to spread also creates a critical vulnerability.
The altered fat composition leaves the cells highly sensitive to ferroptosis – a specialised form of programmed cell death triggered by toxic lipid damage and iron accumulation. Dr Moon describes this as the cancer’s “Achilles’ heel”.
“The cancer cells essentially create their own weakness,” Dr Moon explained. “The very changes that help them metastasise also make them uniquely vulnerable to ferroptosis. We want to exploit that vulnerability therapeutically.”
The research programme will investigate how MAFF contributes to the biological and metabolic mechanisms that enable cancer cells to spread and survive in distant organs during metastasis. Using advanced experimental approaches, the team aims to better understand how tumour cells adapt to different tissue environments and to identify vulnerabilities that could be therapeutically targeted. By uncovering key processes that support metastatic disease, the work seeks to inform the development of new strategies for cancer treatment.
“Metastatic breast cancer is still responsible for the vast majority of breast cancer deaths,” said Dr Moon. “We hope this research will help us develop therapies that target the unique vulnerabilities of spreading cancer cells and ultimately improve outcomes for patients.”
The project highlights the growing importance of cancer metabolism research and the role of lipid biology in understanding how tumours evolve, survive and spread.