The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and—in specific geographic regions—erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743

“…Despite being included in some treatment guidelines, bevacizumab added to platinum plus pemetrexed chemotherapy is not J o u r n a l P r e -p r o o f currently approved by regulators. 47 The prolonged survival and increased durability of response observed with first-line nivolumab plus ipilimumab in unresectable MPM in CheckMate 743, together with subsequent approval of this regimen, demonstrate that significant progress has been made. 14,47 Several studies with immunotherapy-based regimens are ongoing in MPM and will provide further insights into treatment of this disease.…”

“…47 The prolonged survival and increased durability of response observed with first-line nivolumab plus ipilimumab in unresectable MPM in CheckMate 743, together with subsequent approval of this regimen, demonstrate that significant progress has been made. 14,47 Several studies with immunotherapy-based regimens are ongoing in MPM and will provide further insights into treatment of this disease. 31,[48][49][50][51] In conclusion, with an additional year of follow-up, these 3-year data from CheckMate 743 confirm nivolumab plus ipilimumab as a standard of care treatment for unresectable MPM regardless of histology.…”

Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial

“…1 A, we have listed all the genes and related pathways associated with the considered miRNAs. Most of them were connected to cancer development, metabolism and inflammation: all are important pathways activated in mesothelioma development and progression [ 10 ].…”

Artichoke Phytocomplex Modulates Serum microRNAs in Patients Exposed to Asbestos: A First Step of a Phase II Clinical Trial

“…1A, we have listed all the genes and related pathways associated with the considered miRNAs. Most of them were connected to cancer development, metabolism and in ammation: all are important pathways activated in mesothelioma development and progression [10].…”