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The Humane Research Trust funded a research project to understand the cellular mechanisms that enable cancers to progress. Researchers at Edge Hill University have uncovered a gene that seems to play a key role in the mechanism of programmed cell death. This research will help scientists develop target areas for more effective cancer treatments.
Usually, cells form through growth and division, and replace old cells. Cancer disrupts this process. In cancer cases, abnormal cells grow and divide, spreading into surrounding tissue and interfering with essential bodily functions. Cancer cells survive due to defects in a 'apoptosis', which is a universal, in-built programmed cell death mechanism. Normally, this mechanism protects against disease by eliminating abnormal cells, preventing cells with defects from multiplying.
In tumours, however, this mechanism does not function correctly. Studies show that a gene called PERP, which plays a key role in apoptosis, is present at much lower levels in the cells of aggressive tumours. This means that abnormal cells, which the body usually eliminates, end up surviving. There are also links between tumours and inflammation, which can exacerbate the phenomenon of abnormal cell survival.
Before we can develop effective treatments for cancer, we need to understand how genes like PERP can affect apoptosis. Previous research into this area has involved a range of animal experiments. However, the precise function of PERP in the mechanism of apoptosis is still largely unknown.
Between 2022 and 2025, The Humane Research Trust funded a cancer research project to shed light on this phenomenon. The project was led by Luminita Paraoan, Professor of Molecular Cell Biology at Edge Hill University. “We feel that the use of in vitro cellular models offers many advantages over animal-based approaches,” says Prof Paraoan. “These models provide a reliable and reproducible biological background and unlimited material. This gives us the opportunity to study the role of PERP in different cell types and contexts simultaneously.”
The team of researchers used several cell-based experimental models for their study. These models helped them investigate how PERP interacts with mediators of inflammation in live cancer cells. “We hoped to reveal novel targets that scientists can exploit for the development of cancer therapies,” says Prof Paraoan. “These treatments could increase the ability of cancer cells to undergo apoptosis, enhancing their response to radio- and chemotherapy.”
As a result of this work, the scientists have uncovered previously unknown fundamental mechanisms of cell survival in uveal melanoma. They found that PERP is involved in modulation of the cancer-related inflammatory response. This protein also engages in "crosstalk" with various key protein regulators of the pathway associated with inflammation.
Lower levels of PERP is associated with the aggressive form of this cancer and heavily contributes to poor patient outcomes. As a result, the findings from this study have made a substantial contribution to our understanding of uveal melanoma and the importance of PERP in cancer progression. Hear from Prof Paraoan and Dr Grimes about their work, and how funding from the Trust helped them lead the way towards animal-free innovation in the ocular cancer research field.
