New model for understanding patients with asbestos cancer

A team of researchers from the University of Edinburgh has developed a new cell model for studying pleural mesothelioma (PM), a cancer of the lung tissue lining.

Their research indicates that patients with pleural mesothelioma can be categorised into distinct groups, which could lead to more personalised treatments in the future and, hopefully, better outcomes for patients. The new cell model of PM creates the opportunity for further studies into this rare but fatal cancer.

Pleural Mesothelioma - Asbestos Cancer

Pleural mesothelioma (PM) is a rare cancer in the lining of the lung, associated with asbestos exposure. Unfortunately, patients with this disease have very limited options for treatment. Only approximately half of patients diagnosed with PM can expect to survive longer than one year after diagnosis, with current treatments generally extending survival by just a matter of months.

Pleural mesothelioma patients are often diagnosed at a late stage, when the cancer has already progressed and treatment is difficult. Currently, there are no effective curative treatments available.

Creating a new model

A research group from the Centre for Inflammation Research, led by Dr Carsten Hansen, set out to learn more about the drivers of PM. They analysed the biggest PM patient datasets to date, examining records from 298 patients. Through this analysis, they discovered that PM patients can be sorted into separate groups, depending on mutations of specific genes. They furthermore identified that patients with particular mutations have a worse prognosis.

To study this in the laboratory, the team of scientists identified cell mutations that are usually present in PM patients, and engineered these mutations into non-cancerous mesothelial cells. They thereby developed a cancer cell model that can represent specific groups of mesothelioma patients.

This new model will allow researchers to explore the fundamental changes in PM cancer cells caused by the specific mutations and might allow for the development of personalised treatments.

"Currently, there are no curative treatments for pleural mesothelioma, but we are excited about our findings, and hope that our work will have direct impact on future patients."

Dr Carsten Hansen

The NF2 Gene

Using this new model, the research group showed that mesothelioma patients can be grouped on the cellular level and also based upon which gene mutations they have.

They focused on the mutated gene, NF2 (also known as Merlin), a protein frequently lost in PM, which can act to sense the physical environment around the cell. This is important as the environment in which a tumour arises and progresses is markedly distinct from regular tissue.

The researchers predict that the loss of NF2 allows for unconstrained tumour growth.

The future of pleural mesothelioma research

This new discovery sheds light on how mesothelioma is not just one disease, but can be grouped into different patient populations. Specific grouping of PM patients could allow for more effective, personalised medicine approaches in the future.

“We have developed a platform to build on our fundamental understanding of pleural mesothelioma and its molecular underpinnings. Our hope is that we can harness this system to its fullest to fast track the discovery of personalised treatments to deliver to those in need.”

Dr Richard Cunningham

The development of a cellular model system that reflects PM in patients is a powerful experimental tool that could reveal new future treatment targets and insights into the disease.

This work was funded by Worldwide Cancer Research, and at the early stages by The June Hancock Mesothelioma Research Fund.

 

Richard Cunningham, Siyang Jia, Krishna Purohit, Omar Salem, Ning Sze Hui, Yue Lin, Neil O. Carragher, and Carsten Gram Hansen (2023) YAP/TAZ activation predicts clinical outcomes in mesothelioma and is conserved in in vitro model of driver mutations. Clinical and Translational Medicine. https://doi.org/10.1002/ctm2.1190

 

Find out more

Dr Carsten Gram Hansen

Journal article published in Clinical and Translational Medicine

Worldwide Cancer Research

The June Hancock Mesothelioma Research Fund