Genomics and Functional Genomics of Malignant Pleural Mesothelioma

Abstract

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.

Streptococcus australis and Ralstonia pickettii as Major Microbiota in Mesotheliomas

“…Therefore, since the bacterial flora involved in the onset of mesothelioma has been identified, it may be possible to prevent the onset of mesothelioma in future clinical applications by controlling these two species. In particular, asbestos inhalation is a known cause of mesothelioma, and the prevention of mesothelioma is particularly important in high-risk populations exposed to asbestos [ 10 ]. The establishment of a probiosis model, with antimicrobial or vaccine therapy targeting the two target species identified in this study, may serve as a treatment regime for the prevention of the onset of mesothelioma.…”

“…Epidemiologically, mesothelioma is strongly correlated with asbestos inhalation and, since its onset, is usually observed approximately 40 years after asbestos inhalation. As of 2020, it is being increasingly reported worldwide [ 10 ]. Therefore, there is an urgent need to clarify its pathophysiology and establish methods for preventing its onset, as well as to introduce new treatments [ 11 , 12 ].…”

Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients

“…They maintained the same characteristics during several passages in vivo as well as the doubling time that remained stable from the second passage on. They represent, therefore, a good proxy to study new possible interventions and new targeted therapies on the basis of available evidence arising from the molecular characterization of MPM tumors [ 12 , 13 , 49 , 50 , 51 ].…”

Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma

“…However, the standard combination of cisplatin and pemetrexed chemotherapy agents [ 6 ] prolongs the median survival time by approximately 3 months only [ 7 ]. In the last years, genetic studies on MPM reported a low prevalence of oncogene driver mutations and low tumor mutational burden, but frequent copy-number losses and recurrent somatic mutations in oncosuppressor genes such as BAP1, NF2, and CDKN2A [ 8 , 9 , 10 , 11 , 12 , 13 ]. Unfortunately, no targeted therapies exploiting these alterations have emerged.…”