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 Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

2021 ◽  
Vol 22 (16) ◽  
pp. 9014
Author(s):  
Daniela Lisini ◽  
Sara Lettieri ◽  
Sara Nava ◽  
Giulia Accordino ◽  
Simona Frigerio ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Local Drug Delivery ◽  
Pleural Mesothelioma ◽  
Therapeutic Approaches ◽  
Cell Therapies ◽  
Complex Interactions ◽  
Biologic Effects ◽  
Drug Doses ◽  
Lower Drug

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.

scholarly journals ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma

2020 ◽  
Vol 55 (6) ◽  
pp. 1900953 ◽  
Author(s):  
Arnaud Scherpereel ◽  
Isabelle Opitz ◽  
Thierry Berghmans ◽  
Ioannis Psallidas ◽  
Markus Glatzer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malignant Pleural Mesothelioma ◽  
European Society ◽  
Radical Surgery ◽  
Task Force ◽  
Performance Status ◽  
Clinical Importance ◽  
Poor Performance Status ◽  
Pleural Mesothelioma ◽  
European Respiratory Society

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009–2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.

Treatment of malignant pleural mesothelioma: current status and future directions

2011 ◽  
Vol 1 (7) ◽  
pp. 999-1018 ◽  
Author(s):  
Paolo Andrea Zucali ◽  
Rita De Sanctis ◽  
Fabio De Vincenzo ◽  
Matteo Simonelli ◽  
Elena Lorenzi ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Current Status ◽  
Pleural Mesothelioma ◽  
Future Directions

scholarly journals ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma

2020 ◽  
Vol 58 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Isabelle Opitz ◽  
Arnaud Scherpereel ◽  
Thierry Berghmans ◽  
Ioannis Psallidas ◽  
Markus Glatzer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malignant Pleural Mesothelioma ◽  
European Society ◽  
Radical Surgery ◽  
Task Force ◽  
Performance Status ◽  
Clinical Importance ◽  
Poor Performance Status ◽  
Pleural Mesothelioma ◽  
European Respiratory Society

Abstract The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009–2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient’s performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.

scholarly journals Identification of Potential Hub Genes and Therapeutic Drugs in Malignant Pleural Mesothelioma by Integrated Bioinformatics Analysis

2020 ◽  
Vol 43 (12) ◽  
pp. 656-671
Author(s):  
Xiangxin Zhang ◽  
Liu Yang ◽  
Wei Chen ◽  
Ming Kong
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Bioinformatics Analysis ◽  
Asbestos Exposure ◽  
Receptor Interaction ◽  
Pleural Mesothelioma ◽  
Hub Genes ◽  
The Impact

<b><i>Introduction:</i></b> Malignant pleural mesothelioma (MPM) is closely linked to asbestos exposure and is an extremely aggressive tumor with poor prognosis. <b><i>Objective:</i></b> Our study aimed to elucidate hub genes and potential drugs in MPM by integrated bioinformatics analysis. <b><i>Methods:</i></b> GSE42977 was download from the Gene Expression Omnibus (GEO) database; the differentially expressed genes (DEGs) with adj.<i>p</i> value &#x3c;0.05 and |logFC| ≥2 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by DAVID database. The STRING database was used to construct a protein-protein interaction network, and modules analysis and hub genes acquisition were performed by Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to assess the impact of hub genes on the prognosis of MPM patients. The Drug-Gene Interaction database (DGIdb) was used to select the related drugs. <b><i>Results:</i></b> A total of 169 upregulated and 70 downregulated DEGs were identified. These DEGs are enriched in the pathway of extracellular matrix-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and PPAR signaling pathway. Finally, 10 hub genes (CDC20, CDK1, UBE2C, TOP2A, CCNB2, NUSAP1, KIF20A, AURKA, CEP55, and ASPM) were identified, which are considered to be closely related to the poor prognosis of MPM. In addition, 119 related drugs that may have a therapeutic effect on MPM were filtered out. <b><i>Conclusion:</i></b> These discovered genes and small-molecule drugs provide some new ideas for further research on 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.

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