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Understanding how cancer develops

Project title:  Cell survival: what goes wrong in cancer and what should be modulated in therapeutic interventions
University:  Edge Hill University
Principal investigator:  Professor Luminita Paraoan
Co-investigator:  Post Doc Dr Daniel Grimes
Project timescale:  August 2022 - February 2025

The Humane Research Trust is funding 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.

Professor Luminita Paraoan and Dr Daniel Grimes, Edge Hill University
Professor Luminita Paraoan and Dr Daniel Grimes, Edge Hill University

How does cancer develop?

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.

Illustration showing the development and progression of cancer through acquisition of hallmarks of cancer
The development and progression of cancer through acquisition of hallmarks of cancer. Healthy cells regularly divide and undergo programmed cell death, as exampled by the healthy epithelial cell. As the cancer progresses, these cells acquire 'hallmarks of cancer,' specific traits which enable them to grow uncontrollably. DNA damage favouring uncontrolled growth leads to the cells acquiring more and more hallmarks of cancer. This ultimately causes clusters of cancer cells, and eventually metastasis.

An animal-free future for cancer research

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.

The Humane Research Trust is currently funding a cancer research project to shed light on this phenomenon. The project is 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 have built several cell-based experimental models for their study. These models help them investigate how PERP interacts with mediators of inflammation in live cancer cells. “We hope 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.”

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