Malignant pleural mesothelioma is a highly aggressive cancer that is notoriously difficult to treat. Patients diagnosed with the rare asbestos-related disease generally six to 21 months after diagnosis, a survival rate that has not changed for decades. A group of researchers from the Imperial College in London investigated a novel approach to treating the disease and believe they have identified a promising new target for scientists to pursue.
Researchers Examine Fibroblasts’ Role in Mesothelioma Drug Resistance
The researchers from Imperial College noted that mesothelioma treatment has not seen the same benefit from the use of targeted therapies that has been true of other lung malignancies. They attribute this to the fact that cancer-associated fibroblasts in mesothelioma go beyond boosting tumor progression; they also regulate the biology of the tumor cells.
Because there has been little research into studying the crosstalk between the mesothelioma cells and these lung fibroblasts, they decided to pursue this line of inquiry by using cultures from several different mesothelioma cell lines and fibroblasts and then characterizing changes in their secretions and progression.
Targetable Molecular Changes Found in Mesothelioma and Fibroblast Interaction
The investigators revealed recurring targetable molecular changes that were specifically associated with the interaction between the malignant pleural mesothelioma cells and their associated activated fibroblasts. They then tested a variety of novel drug combinations to interrupt this communication and found that the drugs they tested were more effective than the current first-line treatment of cisplatin and pemetrexed.
The group concluded by noting that using an AI-based network propagation, they found that saracatinib extended the survival of the genetically engineered mouse model they were working with far beyond what is usually expected. They wrote, “In conclusion, this research has identified clinically actionable signaling crosstalk between malignant pleural mesothelioma cells and activated fibroblasts that triggers phenotypes associated with disease progression. Compounds targeting the various signaling changes are available and their combination shows superior efficacy in vitro to that of current standard of care. While additional research is now needed to understand how these could be efficiently translated in the clinic, our findings suggest that these offer hope for the better management of malignant pleural mesothelioma, a disease in urgent need of novel more potent therapeutic strategies.”
If you or someone you love has been diagnosed with malignant pleural mesothelioma, this type of research is essential to making progress in the treatment of this challenging disease. For more information on resources available to you, contact the Patient Advocates at Mesothelioma.net at 1-800-692-8608.
