scholarly journals Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations

2021 ◽  
Vol 10 (11) ◽  
pp. 2470
Author(s):  
Eugenia Lorenzini ◽  
Alessia Ciarrocchi ◽  
Federica Torricelli
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Central Element ◽  
Genetic Alterations ◽  
Chromatin Organization ◽  
Therapeutic Options ◽  
Pleural Mesothelioma ◽  
Industrialized Countries ◽  
Molecular Fingerprints ◽  
And Function

Malignant pleural mesothelioma (MPM) is a clinical emergency of our time. Being strongly associated with asbestos exposure, incidence of this cancer is ramping up these days in many industrialized countries and it will soon start to increase in many developing areas where the use of this silicate derivate is still largely in use. Deficiency of reliable markers for the early identification of these tumors and the limited efficacy of the currently available therapeutic options are the basis of the impressive mortality rate of MPM. These shortcomings reflect the very poor information available about the molecular basis of this disease. Results of the recently released deep profiling studies point to the epigenome as a central element in MPM development and progression. First, MPM is characterized by a low mutational burden and a highly peculiar set of mutations that hits almost exclusively epigenetic keepers or proteins controlling chromatin organization and function. Furthermore, asbestos does not seem to be associated with a distinctive mutational signature, while the precise mapping of epigenetic changes caused by this carcinogen has been defined, suggesting that alterations in epigenetic features are the driving force in the development of this disease. Last but not least, consistent evidence also indicates that, in the setting of MPM, chromatin rewiring and epigenetic alterations of cancer cells heavily condition the microenvironment, including the immune response. In this review we aim to point to the relevance of the epigenome in MPM and to highlight the dependency of this tumor on chromatin organization and function. We also intend to discuss the opportunity of targeting these mechanisms as potential therapeutic options for MPM.

scholarly journals Redefining mesothelioma types as a continuum uncovers the immune and vascular systems as key players in the diagnosis and prognosis of this disease

2018 ◽  
Author(s):  
Nicolas Alcala ◽  
Christophe Caux ◽  
Nicolas Girard ◽  
J.D. McKay ◽  
Francoise Galateau-Salle ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Checkpoint Inhibitors ◽  
Asbestos Exposure ◽  
Continuous Model ◽  
Therapeutic Options ◽  
Molecular Profile ◽  
Pleural Mesothelioma ◽  
Therapeutic Approaches ◽  
Aggressive Disease ◽  
Key Players

SummaryMalignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, which incidence is expected to increase in the future, and with no effective therapeutic options. We have performed unsupervised analyses of publicly available RNAseq data for 297 MPM. We found that the molecular profile and the prognosis of this disease is better explained by a continuous model rather than by the current WHO classification into the epitheloid, biphasic and sarcomatoid histological types. The main source of variation of this continuum was explained by the immune and vascular pathways, with strong differences in the expression of pro-angiogenic genes and immune checkpoint inhibitors across samples. These data may inform future classifications of MPM and may also guide personalised therapeutic approaches for this disease.SignificanceMalignant Pleural Mesothelioma (MPM) is an aggressive disease with no effective therapeutic options. Unsupervised transcriptomic analyses of 297 MPM unveiled the vascular and the immune systems as key players in the prognosis of this disease, and identified potential therapeutic approaches for this disease targeting these pathways.

Asbestos Exposure and Malignant Pleural Mesothelioma in Portugal: a scoping review

2020 ◽  
Vol 30 (Supplement_2) ◽  
Author(s):  
C Santos ◽  
MA Dixe ◽  
E Sacadura-Leite ◽  
P Astoul ◽  
A Sousa-Uva
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Scoping Review ◽  
Case Reports ◽  
Asbestos Exposure ◽  
Cochrane Library ◽  
International Agency ◽  
Pleural Mesothelioma ◽  
Industrialized Countries ◽  
Hospital Data ◽  
Incidence And Mortality

Abstract Introduction Asbestos, widely used for its important chemical and physical characteristics, are recognized in all their varieties as a human carcinogen by the International Agency for Research on Cancer (IARC) and as the leading cause of cancer associated with occupational exposure in industrialized countries. Despite being the most studied occupational hazard since 1965, it is the malignant pleural mesothelioma (MPM), the decisive aspect in the study of the exposure to asbestos. Objectives Make a state of the art of the relationships between asbestos and MPM in Portugal. Methodology A scoping review using the Joanna Briggs Institute (JBI) methodology was conducted using five information’s sources: Pubmed, Web of Science, The Cochrane Library, Scopus and Google Scholar and Open Access Scientific Repositories of Portugal and DART-Europe E-theses Portal to search also for gray literature. Data were collected between 1960-2019, with the keywords "Asbestos" and "Mesothelioma” and “Portugal”. Inclusion criteria were defined for types of participants, concept, context and types of studies. Results Of the 1453 studies reviewed 9 were included. The oldest study is from 1986. Five studies are about incidence and survival, two are case reports, one about exposure and mortality and one about treatment. To analyse incidence and mortality, four authors used hospital data and two the data from the southern regional cancer registry (ROR). In these studies, it is also presented the description of the population in terms of mean age, type of exposure, latency time, histological type and stage. Conclusion Portugal, such as other industrialized countries, used asbestos in a massive way, but despite this, few studies and data on the relationship between asbestos exposure and MPM are found. Dedicated studies are needed to objectively assess the true dimension of this potential problem in Portugal and characterise the different types of exposures related to MPM.

scholarly journals Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1138
Author(s):  
Martina Schiavello ◽  
Elena Gazzano ◽  
Loredana Bergandi ◽  
Francesca Silvagno ◽  
Roberta Libener ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Malignant Pleural Mesothelioma ◽  
Antioxidant Defense ◽  
Asbestos Exposure ◽  
Predictive Biomarkers ◽  
Antioxidant Systems ◽  
Pleural Mesothelioma ◽  
Related Factor ◽  
Aggressive Cancer

Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.

scholarly journals Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Cheng-Kuan Lin ◽  
Yu-Ying Chang ◽  
Jung-Der Wang ◽  
Lukas Jyuhn-Hsiarn Lee
Keyword(s):  
Cohort Study ◽  
General Population ◽  
Incidence Rate ◽  
Malignant Pleural Mesothelioma ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Asbestos Exposure ◽  
Pleural Mesothelioma ◽  
Calendar Period ◽  
Incident Cases

Objective. This paper aimed to determine the standardised incidence ratio (SIR) of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.Methods. All workers employed in asbestos-related factories and registered by the Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were included in the study and were followed from 1 January, 1980, through 31 December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163), were obtained from the Taiwan Cancer Registry. SIRs were calculated based on comparison with the incidence rate of the general population of Taiwan and adjusted for age, calendar period, sex, and duration of employment.Results. The highest SIR of MPM was found for male workers first employed before 1979, with a time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25–8.09). After consideration of duration of employment, the SIR for male MPM was 5.78 (95% CI: 1.19–16.89) for the workers employed for more than 20 years in asbestos-related factories.Conclusions. This study corroborates the association between occupational asbestos exposure and MPM. The highest risk of MPM was found among male asbestos workers employed before 1979 and working for more than 20 years in asbestos-related factories.

Case 13.8

2014 ◽  
pp. 628-629
Author(s):  
Christine U. Lee ◽  
James F. Glockner
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
The United States ◽  
Extrapleural Pneumonectomy ◽  
Parietal Pleura ◽  
Pleural Mesothelioma ◽  
Pleural Plaques ◽  
Abnormal Chest ◽  
Left Pleura ◽  
Histologic Subtypes

62-year-old man with shortness of breath and an abnormal chest CT Axial 3D SPGR postgadolinium images (Figure 13.8.1) demonstrate diffuse thickening and enhancement of the left pleura, with a few minimally enhancing, focal right-sided pleural plaques. Malignant pleural mesothelioma Malignant pleural mesothelioma is a rare neoplasm that originates from the mesothelial cells lining the visceral and parietal pleura. The incidence of malignant pleural mesothelioma in the United States is 15 cases per million; there is a strong correlation with asbestos exposure. Malignant pleural mesothelioma is divided into 3 histologic subtypes: epithelial (55%-65%), sarcomatoid (10%-15%), and mixed (20%-35%). Patients with epithelial malignant pleural mesothelioma have the best prognosis, and among those with limited disease who undergo extrapleural pneumonectomy (removal of the pleura, lung, hemidiaphragm, and part of the pericardium), survival is longer (5-year survival, 39%) than among all patients (median survival, 8-18 months after diagnosis)....

scholarly journals Multimodality treatment of malignant pleural mesothelioma

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1681 ◽  
Author(s):  
Lawek Berzenji ◽  
Paul Van Schil
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Multimodality Treatment ◽  
Treatment Modalities ◽  
Surgical Approaches ◽  
Extrapleural Pneumonectomy ◽  
Pleural Mesothelioma ◽  
Treatment Approaches ◽  
Definitive Answer ◽  
Platinum Based Chemotherapy

Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.

scholarly journals Deep Sequencing Analysis Identified a Specific Subset of Mutations Distinctive of Biphasic Malignant Pleural Mesothelioma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2454
Author(s):  
Federica Torricelli ◽  
Filippo Lococo ◽  
Teresa Severina Di Stefano ◽  
Eugenia Lorenzini ◽  
Simonetta Piana ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Deep Sequencing ◽  
Validation Cohort ◽  
Genetic Alterations ◽  
Pleural Mesothelioma ◽  
Sequencing Analysis ◽  
Specific Subset ◽  
Validation Set ◽  
Custom Panel ◽  
Deep Sequencing Analysis

Malignant Pleural Mesothelioma (MPM) is a heterogeneous disease. Morphologically, three different phenotypes are distinguishable: epithelioid (e-), sarcomatoid (s-) and biphasic (biph-) MPM, the latest, being a mixture of e- and s-MPM cells. Being an intermediate entity, management of biph-MPM, remains debatable and controversial, with different guidelines recommending distinct approaches. Identification of biph-MPM associated genetic alterations, through deep sequencing analysis, may provide useful tools to understand these lesions. A retrospective cohort of 69 surgically resected MPMs, 39 biph-MPMs (56.5%) and 30 e-MPMs (43.5%) was selected. A separate set of 16 biph-MPM was used as validation set. Deep sequencing analysis on an MPM-specific custom panel (MPM_geneset) comprising 1041 amplicons spanning 34 genes was performed. A total of 588 variants and 5309 mutational events were detected. In total, 91.3% of MPMs showed at least one mutation and 76.8% showed co-occurrence of more than one alteration. Mutations in MXRA5 (p = 0.05) and NOD2 (p = 0.018) were significantly associated with biph-MPM both in the training and validation cohort and correlated with the extent of the sarcomatoid component. Mutations in NOD2 and XRCC6 correlated with patients’ survival. We demonstrated that biph-MPM are associated with a specific mutation set, and that genetic analysis at diagnosis may improve patients’ risk stratification.

scholarly journals Treatment of malignant pleural mesothelioma: current status and future directions

2016 ◽  
Vol 73 (2) ◽  
Author(s):  
X. Dhalluin ◽  
A. Scherpereel
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
European Society ◽  
Poor Prognosis ◽  
Asbestos Exposure ◽  
Therapeutic Strategies ◽  
Current Status ◽  
Pleural Mesothelioma ◽  
European Respiratory Society ◽  
Future Directions ◽  
Cell Therapies

Previously considered to be rare, malignant pleural mesothelioma (MPM) is a highly aggressive tumour that has become a very important issue over recent years due to its poor prognosis and its increasing incidence mostly linked to previous asbestos exposure. An optimal treatment for MPM is not established yet; new therapies and predictive tools are still needed in the management of this cancer. Thus the aim of this review is to provide clinicians clear and up-to-dated data on the latest therapeutic strategies for MPM patients in 2010. The guidelines recently proposed by the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) taskforce are summarized here. The authors also briefly reviewed the future directions in MPM treatment including targeted therapies, gene or cell therapies.

scholarly journals Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival

2020 ◽  
Vol 14 (6) ◽  
pp. 1207-1223 ◽  
Author(s):  
Lisa Quetel ◽  
Clément Meiller ◽  
Jean‐Baptiste Assié ◽  
Yuna Blum ◽  
Sandrine Imbeaud ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Tumor Heterogeneity ◽  
Genetic Alterations ◽  
Pleural Mesothelioma
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