Research funded by the National Cancer Institute has identified a protein that might play a key role in survival of pleural mesothelioma.
The protein is called UHRF1. It is encoded by a gene of the same name. Researchers believe it may be a driver of growth and spread in malignant mesothelioma.
The research will have to be confirmed on a larger scale. But if it turns out to be true, it could give doctors a new way to extend survival of pleural mesothelioma.
Finding Drivers of Mesothelioma Growth
Pleural mesothelioma is a membrane (mesothelium) cancer caused by asbestos exposure. Although some people do survive mesothelioma, it is rare. Average survival of pleural mesothelioma is right around 18 months.
It can take decades for mesothelioma to develop after asbestos exposure. Once it does, it typically grows and spreads quickly. Researchers are still trying to understand why this is. If they can isolate drivers of mesothelioma growth, they may be able to slow it down.
According to the NCI scientists, the UHRF1 protein “has emerged as an epigenetic driver in human cancers”. Epigenetic means a non-genetic influence on gene expression. The goal of the new study was to determine whether UHRF1 impacts survival of pleural mesothelioma as it seems to with other cancers. If it does, the next step will be to find ways to regulate it.
Increasing Survival of Pleural Mesothelioma
Researchers started by measuring the UHRF1 level in different kinds of cells. They analyzed UHRF1 in
- normal mesothelial cells
- asbestos-exposed mesothelial cells
- lab-grown pleural mesothelioma cells lines
- normal pleural membrane cells
- cells from pleural mesothelioma patients
“UHRF1 expression was significantly higher in malignant pleural mesothelioma lines and specimens,” states the report in the Journal of Thoracic Oncology. Even the normal mesothelioma cells had higher levels of UHRF1 after asbestos exposure.
Even more importantly, patients with higher UHRF1 had shorter survival of pleural mesothelioma. “The overexpression of UHRF1 was associated with decreased overall survival in patients with MPM,” writes NCI researcher David Schrump.
Researchers experimented with different ways to knock down UHRF1 expression. The chemotherapy drug mithramycin reduced UHRF1 in lab-grown cells and in mice that were infected with pleural mesothelioma. Drugs that raised levels of the tumor suppressor protein p53 also reduced UHRF1.
The researchers concluded that UHRF1 helps mesothelioma tumors grow and that reducing it could improve survival in pleural mesothelioma.
“These findings support the efforts to target UHRF1 expression or activity for mesothelioma therapy,” the study concludes.
Reardon, E, et al, “UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma”, September 11, 2020, Journal of Thoracic Oncology, Epub ahead of print, https://www.jto.org/article/S1556-0864(20)30716-4/fulltext
Moench, S, “UHRF1 May Be an Actionable Target in Malignant Pleural Mesothelioma”, October 8, 2020, Cancer Therapy Advisor, https://www.cancertherapyadvisor.com/home/cancer-topics/lung-cancer/mesothelioma-uhrf1-actionable-target-treatment/