Malignant pleural mesothelioma is a tumor caused by asbestos exposure. Recently, the United States Food and Drug Administration approved immunotherapy treatment for mesothelioma. But the efficacy of available treatments is still limited.
Researchers are still evaluating these new therapeutic approaches. They are also working to identify subgroups of patients who could benefit from precision medicine. Precision medicine uses information about a person’s tumor to find out how well a treatment is working.
One of these groups could be represented by patients with an inherited cancer syndrome. These are caused by germline pathogenic variants (PVs) in DNA repair genes.
A germline pathogenic variant is a gene variant (or mutation) that is passed from parent to child. These germline PVs are hereditary. This means that someone can have an inherited predisposition for cancer.
A new Italian study is the first to confirm that 10% of patients with malignant mesothelioma carry a germline pathogenic variant (PV).
This discovery has many implications. First, it may help to explain why some people develop mesothelioma after asbestos exposure. It is possible that people with this PV are more sensitive to asbestos-mediated cancers.
According to their analysis, patients carrying PVs were more susceptible to asbestos-induced mesothelioma. They need less asbestos exposure to develop mesothelioma.
But more importantly, patients with this PV are perfect candidates for precision medicine. This scenario may be exploited for the development of tailored treatment.
Exploiting Gene-Predisposition for Tailored Treatment
Patients with this inherited germline PVs are evident in other cancers. Other cancer studies have shown that PV patients have an increased sensitivity to drugs.
Patients with mesothelioma carrying germline PVs may benefit from a specific treatment. This treatment uses drugs to create synthetic lethality. Synthetic lethality attacks two genes together to cause cancer cell death.
In conclusion, this new study identifies a subgroup of patients with germline PVs. They are more prone to asbestos-induced cancers. But, they may respond to personalized medicine better.
Sculco, Marika, Marta La Vecchia, Anna Aspesi, Giulia Pinton, Michela G. Clavenna, Elisabetta Casalone, Alessandra Allione et al. “Malignant pleural mesothelioma: Germline variants in DNA repair genes may steer tailored treatment.” European Journal of Cancer 163 (2022): 44-54. https://doi.org/10.1016/j.ejca.2021.12.023