PROGETTO PRIMATE

An integrated precision medicine approach to malignant mesothelioma: from mutation load to epidemiology and therapy

PROJECT SUMMARY

Pleural mesothelioma is caused by asbestos exposure. Malignant mesothelioma has a long latency period. However, some studies reported a large inter-individual variability in the onset, from less than 10 to more than 70 years from asbestos exposure. This variability may be due to difficulties in ascertaining the starting of asbestos exposure or to other factors such as genetic factors or chance. Chronic inflammation elicited by asbestos fibers also seem s to play an important role in the origin of this disease. It increases the aggressiveness of cancer cells promoting the progression of neoplastic clones into advanced disease. To clarify how malignant mesothelioma depends on asbestos exposure and, in turn, to improve our knowledge about disease development and progression, we have planned a multidisciplinary project integrating molecular, epidemiological, and legal aspects. For the present project, the three recruiting partners will enroll a large series of mesothelioma patients and will provide biological materials and clinical data. From the molecular point of view, we will analyse the constitutive genetic variations, the acquired mutations in the tumour, the markers of inflammatory status measurable directly in the blood. We will also analyse asbestos exposure by measuring the number of asbestos bodies in lung tissue, and by collecting data on occupational and environmental exposure to asbestos fibers. Furthermore, we will investigate, in vitro, the eligibility of mesothelioma to the recently developed boron neutron capture therapy. All collected molecular and descriptive data will be integrated in order to define a comprehensive spectrum of markers that can be potentially useful for clinicians to define a more personalized therapeutic care of mesothelioma patients and for the courts to provide an help in assessment of causation in asbestos trials.