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Science
2024 results

JULY 2024
RESULTS ARE IN!

Erase meso mesothelioma research charity
erase meso funds meso UK research project

Commissioned Research Successful

Latest research study leverages a new class of cancer target for mesothelioma diagnosis and treatment

 

Identifies MDIG as a potential drug target for the development of future asbestos-related cancer treatment

 

A six-month research project, supported by national charities, Mesothelioma UK and Erase Meso, has discovered a significant advancement in the diagnosis and treatment of the asbestos-related cancer, mesothelioma.

 

Funded by Erase Meso, the project aimed to leverage a new class of cancer target to benefit patients suffering from this aggressive cancer.

Scientist

Funding a Meso
UK Research
Project

erase meso mesothelioma research UK
erase meso funds meso UK research project

The project was a collaboration between Professor Mathew Coleman at the University of Birmingham and Professors Marion MacFarlane and Anne Willis OBE at the MRC (Medical Research Council) Toxicology Unit at the University of Cambridge, Professor John Le Quesne (CRUK Beatson Institute, Glasgow) and Professor Christopher Schofield (University of Oxford).

Erase Meso donated a financial grant of £37,973 and found a new class of cancer target for the benefit of mesothelioma (asbestos-related cancer) diagnosis and treatment. The project analysed the enzyme MDIG (Mineral Dust Induced Gene) that is known to be altered in the lungs of those in contact with mineral dust like silica. MDIG is over-represented in mesothelioma cells.

The research team focused on an enzyme known as 'MDIG', a type of oxygenase that acts as a cellular switch using oxygen. While MDIG is known to be persistently active in several tumour types, its role in mesothelioma had not been previously explored. Given MDIG's influence on protein synthesis, which is a critical process for mesothelioma survival, and its increased levels due to exposure to silica and mineral dusts, researchers hypothesised that MDIG might significantly contribute to mesothelioma development.

 

The team discovered high levels of MDIG and its cellular targets in laboratory-grown mesothelioma cells. Furthermore, they found that the enzyme's activity and function are essential for the rapid growth of these cells. These findings suggest that MDIG could be a promising new drug target for mesothelioma treatment. The research team is now well-positioned to target MDIG through their collaborations with chemists at the University of Oxford and Rome.

 

Mathew Coleman, Professor in Tumour Cell Biology at the Institute of Cancer and Genomic Sciences at the University of Birmingham commented: "This research suggests that MDIG is a potential drug target for the development of future mesothelioma treatment strategies.

 

“In the short term, it rationalises further studies into the role of MDIG in mesothelioma cells and the development of next-generation MDIG inhibitors. In the longer term, it supports preclinical studies that could ultimately be translated into the clinic for improved patient survival and quality of life. Huge thanks to Erase Meso and Mesothelioma UK for supporting the project!"

 

Paul Cook, founder of Erase Meso said: “I am immensely proud of the strides we are making in the fight against mesothelioma. This groundbreaking research on MDIG represents a beacon of hope for patients and their families who have been affected by this devastating disease. At Erase Meso, we are dedicated to supporting innovative research that has the potential to transform diagnosis and treatment options for mesothelioma. Our collaboration with Mesothelioma UK and esteemed researchers like Professor Mathew Coleman underscores our commitment to finding a cure and improving the quality of life for all those affected. We are hopeful that this discovery will pave the way for new, effective treatments and ultimately, a future free from mesothelioma."

 

Liz Darlison, Chief Executive of Mesothelioma UK added: “By identifying this new drug target, we have the potential to extend the possible treatment options for mesothelioma patients. Our thanks go to Mathew and his research team for their dedicated work, and to Erase Meso for their continued commitment to supporting research into mesothelioma treatment and care.”

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End of Study Report

 

"Leveraging a new class of cancer target for the benefit of mesothelioma diagnosis and treatment"

Study Summary

We investigated a type of enzyme that uses oxygen to act as a kind of switch in cells (a so called ‘oxygenase’). Although this enzyme switch is known to be stuck on in several different tumour types, it had not previously been studied in the context of mesothelioma.

Because this enzyme is known to play a role in biology that was recently shown to be important to mesothelioma survival (protein synthesis), and its levels are induced by silica and mineral dusts, we hypothesised that it may play a role in mesothelioma development. We discovered that there is lots of this enzyme and its cellular targets in mesothelioma cells grown in the laboratory, and that the activity and function of the enzyme is required for mesothelioma growth and viability. Our data suggest that this enzyme is a new candidate drug target for mesothelioma treatment, which we can develop through our work with the University of Oxford and Rome on the first drugs that target this enzyme.

Impact

 

This research has confirmed that MDIG is a potential drug target for the development of future mesothelioma treatment strategies. In the short term it rationalises further studies into the role of MDIG in mesothelioma cells and the development of next generation MDIG inhibitors.

In the longer term it supports preclinical studies that model MDIG inhibition and combination therapies that could ultimately be translated into the clinical for improved patient survival and quality of life.

This grant has validated the original hypothesis and build a dataset that can be used to apply for more substantial funding in the future.

We'd like to thank everyone involved in this successful project..and especially our supporters for funding it

if you'd like to donate to further research please donate here..

Science Lab

More information

A more indepth description of the Study.

Study Findings

Please provide details of your key study findings.Please try to limit to two A4 sheets of paper

 

This was a short pump priming grant, originally for 6 months. The original project was to fund our resident MDIG expert Dr Regina Andrijes, who had all the skills and experience required to hit the ground running. Unfortunately, because of the delays to the award, Regina had to leave the lab and find another job. In the end we had to appoint a different post-doc without the same level of experience, which required a period of training that delayed progress. Despite this, we were able to establish several mesothelioma cell lines in our lab from Marion MacFarlane (Cambridge). We characterised these for expression of MDIG, Rpl27a, and Nucleophosmin, finding that each of these proteins was highly expressed in mesothelioma tumour cell lines. To complement this, we collaborated with John Le Quesne (Glasgow) to develop a new multiplex immunohistochemical assay for MDIG, nucleophosmin, and Ki67 (and nuclear counterstain with Hoechst). This assay will be applied to mesothelioma tissue microarrays from Marion MacFarlane. We then developed a protein translation rate assay in mesothelioma cell lines using puromycin incorporation and an anti-puromycin antibody and discovered that MDIG expression levels correlate with protein translation rate in mesothelioma tumour cell lines. Next, we developed a doxycycline-inducible shRNA knockdown model of MDIG loss of function in 3 mesothelioma cell lines with the highest levels of MDIG expression. To do so we established lentivirally transduced puromycin resistant control, MDIG#1, and MDIG#3 shRNA cells in each of the 3 mesothelioma tumour cell lines. Following validation of successful doxycycline-inducible MDIG knockdown, we undertook growth and viability assays to determine the effect of MDIG inhibition on mesothelioma cell lines. Consistent with the original hypothesis, we found that MDIG knockdown slowed the growth and reduced the viability of mesothelioma cell lines. Similar results were obtained with MDIG inhibitors.

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