Aravind Malireddy and Bill Tawil*

Department of Biotechnology and Bio Informatics, California State University Channel Islands, University Drive, Camarillo, 93010, CA, USA

*Corresponding Author: Bill Tawil, Department of Biotechnology and Bio Informatics, California State University Channel Islands, University Drive, Camarillo, 93010, CA, USA.

Received: January 27, 2025; Published: April 07, 2025

Abstract

Malignant mesothelioma is an aggressive cancer predominantly caused by asbestos exposure, yet it also has strong genetic underpinnings. This review provides an in-depth exploration of the genetic factors, such as BAP1 mutations, AQP1 polymorphisms, and other hereditary influences that increase susceptibility to mesothelioma. The role of environmental exposure, particularly to asbestos and erionite, is also examined, highlighting the synergistic effects of genetics and environmental risk factors in disease development.

Recent advances in therapeutic approaches are critically evaluated, including traditional treatments like chemotherapy and innovative therapies such as immunotherapy, gene therapy, and CAR T-cell therapy. Key clinical trials, including the MAPS trial, which combined pemetrexed cisplatin with bevacizumab, showed improved overall survival rates for patients with unresectable pleural mesothelioma. The review also delves into photodynamic therapy and the growing promise of immune checkpoint inhibitors such as nivolumab and ipilimumab, which have demonstrated encouraging results in extending progression-free survival and overall survival. The potential of dendritic cell-based therapies and gene therapy, particularly the intrapleural transfer of interferon-alpha, are explored as novel strategies in mesothelioma management.

Despite the promising advances in treatments, mesothelioma remains challenging to treat effectively. This review emphasizes the importance of continued research into both genetic predispositions and targeted therapies. A combination of personalized medicine, focusing on genetic mutations, and the development of therapies tailored to specific patient profiles could pave the way for more effective and durable treatment outcomes for mesothelioma patients.

 Keywords: Mesothelioma; Asbestos; Pleural Mesothelioma; Peritoneal Mesothelioma; BAP1 Gene; Immunotherapy; Chemotherapy; Gene Therapy; Clinical Trials; Targeted Therapy; CAR T-Cell Therapy; Intra Pleural Gene Transfer

References

1. Obacz Joanna., et al. “Biological Basis for Novel Mesothelioma Therapies”. British Journal of Cancer8 (2021): 1039-1055.
2. Ziółkowska Barbara., et al. “Systemic Treatment in Patients with Malignant Pleural Mesothelioma - Real Life Experience”. BMC Cancer1 (2022).
3. Hiltbrunner S., et al. “Tumor immune microenvironment and genetic alterations in mesothelioma”. Frontiers in Oncology 11 (2021): 660039.
4. Cleaveland clinic “what is mesothelioma”.
5. http://www.cancerresearchuk.org/aboutcancer/mesothelioma/stages
6. Moncivais Katy and linda Molinari. “Mesothelioma Cancer”.
7. Yang Haining., et al. “Mesothelioma Epidemiology, Carcinogenesis, and Pathogenesis”. Current Treatment Options in Oncology2-3 (2008): 147-157.
8. Noonan Curtis W. “Environmental Asbestos Exposure and Risk of Mesothelioma”. Annals of Translational Medicine11 (2017): 234-234.
9. Maule Milena Maria., et al. “Modeling Mesothelioma Risk Associated with Environmental Asbestos Exposure”. Environmental Health Perspectives7 (2007): 1066-1071.
10. Muzaffer Metintas., et al. “Environmental Asbestos Exposure and Malignant Pleural Mesothelioma”. Respiratory Medicine5 (1999): 349-355.
11. Sahmel J., et al. “Evaluation of Take-Home Exposure and Risk Associated with the Handling of Clothing Contaminated with Chrysotile Asbestos”. Risk Analysis8 (2014): 1448-1468.
12. Peipins Lucy A., et al. “Radiographic Abnormalities and Exposure to Asbestos-Contaminated Vermiculite in the Community of Libby, Montana, USA”. Radiographic Abnormalities and Exposure to Asbestos-Contaminated Vermiculite in the Community of Libby, Montana, US14 (2003): 1753-1759.
13. Pan Xue-lei., et al. “Residential Proximity to Naturally Occurring Asbestos and Mesothelioma Risk in California”. American Journal of Respiratory and Critical Care Medicine8 (2005): 1019-1025.
14. Madkour MT., et al. “Environmental Exposure to Asbestos and the Exposure-Response Relationship with Mesothelioma”. Eastern Mediterranean Health Journal1 (2009): 25-38.
15. Corfiati Marisa., et al. “Epidemiological Patterns of Asbestos Exposure and Spatial Clusters of Incident Cases of Malignant Mesothelioma from the Italian National Registry”. Epidemiological Patterns of Asbestos Exposure and Spatial Clusters of Incident Cases of Malignant Mesothelioma from the Italian National Registry1 (2015).
16. Amin Waqas., et al. “Factors Influencing Malignant Mesothelioma Survival: A Retrospective Review of the National Mesothelioma Virtual Bank Cohort”. F1000Research 7 (2019).
17. Louie Bryan H and Razelle Kurzrock1. “BAP1: Not Just a BRCA1-Associated Protein”. (2020): 1-23.
18. Panou Vasiliki and Oluf Dimitri Røe. “Inherited Genetic Mutations and Polymorphisms in Malignant Mesothelioma: A Comprehensive Review”. International Journal of Molecular Sciences12 (2020): 4327.
19. Pinton Giulia., et al. “CDKN2A Determines Mesothelioma Cell Fate to EZH2 Inhibition”. Frontiers in Oncology 11 (2021).
20. Hmeljak Julija., et al. “Integrative Molecular Characterization of Malignant Pleural Mesothelioma”. Cancer Discovery12 (2018): 1548-1565.
21. “Epigenetic Regulation of MiRNA Expression in Malignant Mesothelioma: MiRNAs as Biomarkers of Early Diagnosis and Therapy”. 28 (2019): 1-14.
22. Bononi Angela., et al. “BAP1 Is a Novel Regulator of HIF-1α”. Proceedings of the National Academy of Sciences of the United States of America4 (2023).
23. Wu Licun and Marc de Perrot. “Omics Overview of the SPARC Gene in Mesothelioma”. Biomolecules7 (2023): 1103.
24. “Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study”.
25. Senk Barbara., et al. “Genetic Polymorphisms in Aquaporin 1 as Risk Factors for Malignant Mesothelioma and Biomarkers of Response to Cisplatin Treatment”. Radiology and Oncology1 (2019): 96-104.
26. Gupta Sounak., et al. “Assessment of Risk of Hereditary Predisposition in Patients with Melanoma And/or Mesothelioma and Renal Neoplasia”. JAMA Network Open11 (2021): e2132615-e2132615.
27. Malignant Mesothelioma Market: Epidemiology, Industry Trends, Share, Size, Growth, Opportunity, and Forecast 2024-2034, Report ID: SR112024A9205.
28. Malignant Mesothelioma Market Size, Share, Growth, and Industry Analysis, By Type (Oral and Parenteral), By Application (Hospital Pharmacies, Retail Pharmacies, Oncology Centres, and Others), Regional Insights, and Forecast To 2032, Report ID: BRI106151.
29. Mesothelioma Treatment Market Size, Share, Growth, Trends, and Global Industry Analysis: By Drug Class (Alkylating Agents, Antimetabolites, Plant Alkaloids, Antitumor Antibiotics, and Others), By Application (Pleural Mesothelioma and Peritoneal Mesothelioma), By Route of Administration (Oral and Parenteral), By Distribution Channel (Hospital Pharmacies, Retail Pharmacies, and Online Pharmacies), and Region.
30. “Mesothelioma Treatment Market Growth Status, Global Size, Share, Emerging Trends and Key Players Outlook to 2028”.
31. “Malignant Mesothelioma - Market Insight, Epidemiology And Market Forecast – 2032”. Published Date : Dec 2022, Region : United States, EU5, Japan.
32. “Global Nivolumab Market - Industry Trends and Forecast to 2030”.
33. “Malignant Mesothelioma Market Size to Reach USD 12.2 Billion by 2034, Impelled by Increasing Popularity of Gene Therapy”. August 5, (2024).
34. “Malignant mesothelioma, therapeutics market size share industry forecast and outlook (2024 to 2031)”. published October 2024, SKU:PH5147.
35. Malignant Pleural Mesothelioma Market Drug Class (Premetrexed and Combination, Cisplatin and Combination, Carboplatin and Combination, Gemcitabine and Combination, Vinorelbine and Combination and Other Combination), By Route of Administration (Oral and Parenteral), By Distribution Channel (Hospital Pharmacies, Retail Pharmacies, Oncology Centers), By Region (North America, Europe, Asia Pacific, Latin America, and Middle East & Africa); Trend Analysis, Competitive Market Share & Forecast, 2016-26, Published Date: March 2020, Report ID: BWC19437.
36. “Global Malignant Mesothelioma Market Size, Scope And Forecast Report”. Report ID: 1014581 | Published: October 2024 | Study Period: 2021-2031.
37. Tsao Anne S., et al. “New Era for Malignant Pleural Mesothelioma: Updates on Therapeutic Options”. Journal of Clinical Oncology 5 (2022).
38. Darya Karatkevich., et al. “Schedule-Dependent Treatment Increases Chemotherapy Efficacy in Malignant Pleural Mesothelioma”. International Journal of Molecular Sciences19 (2022): 11949-11949.
39. Zauderer Marjorie G., et al. “Vinorelbine and Gemcitabine as Second- or Third-Line Therapy for Malignant Pleural Mesothelioma”. Lung Cancer3 (2014): 271-274.
40. Darya Karatkevich., et al. “Chemotherapy Increases CDA Expression and Sensitizes Malignant Pleural Mesothelioma Cells to Capecitabine Treatment”. Scientific Reports1 (2024).
41. Banks Kian C., et al. “Comparison of Survival by Multimodal Treatment Regimen among Malignant Pleural Mesothelioma Patients in an Integrated Health System”. Clinical Lung Cancer8 (2022): 694-701.
42. Chiec Lauren and Debora S Bruno. “Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies”. International Journal of Molecular Sciences19 (2024): 10861.
43. Xiaotong Guo., et al. “Immunotherapy vs. Chemotherapy in Subsequent Treatment of Malignant Pleural Mesothelioma: Which Is Better?” 27 (2023): 1-24.
44. Adusumilli Prasad S., et al. “A Phase I Trial of Regional Mesothelin-Targeted CAR T-Cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab”. Cancer Discovery11 (2021).
45. Federica Borea., et al. “Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?” International Journal of Molecular Sciences11 (2023): 9165-9165.
46. Kondo Nobuyuki and Seiki Hasegawa. “Optimal Surgery for Resectable Malignant Pleural Mesothelioma in the Setting of Multimodality Treatment”. Surgery Today (2023).
47. Chapman Evelina and Marcelo García Diéguez. “Radiotherapy for Malignant Pleural Mesothelioma”. Cochrane Database of Systematic Reviews 19 July (2006).
48. Luna Javier., et al. “GOECP/SEOR Clinical Guidelines on Radiotherapy for Malignant Pleural Mesothelioma”. World Journal of Clinical Oncology8 (2021): 581-608.
49. Intrapleural Gene Transfer for Pleural Mesothelioma (IFN-alpha), 2015-09-22, identifier: NCT01212367.
50. Chintala Navin K., et al. “CAR T-Cell Therapy for Pleural Mesothelioma: Rationale, Preclinical Development, and Clinical Trials”. Lung Cancer (Amsterdam, Netherlands) 157 (2021): 48-59.
51. “Mesothelioma Avastin Plus Pemetrexed-cisplatin Study (MAPS)”. NCT00651456. Intergroupe Francophone de Cancerologie Thoracique. 2008-03-29.
52. “A Study of Immunotherapy Drugs Nivolumab and Ipilimumab in Patients w/Resectable Malignant Peritoneal Mesothelioma”. NCT05041062. University of Chicago. 2021-09-07.
53. CAR T Cells in Mesothelin Expressing Cancers. NCT03054298. University of Pennsylvania. 2017-02-09.
54. “Intrapleural Photodynamic Therapy in a Multimodal Treatment for Patients With Malignant Pleural Mesothelioma (MesoPDT)”. NCT02662504. University Hospital, Lille. 2016-01-14.
55. “Clinical and Histopathologic Characteristics of BAP1 Mutations”. NCT01773655. Memorial Sloan Kettering Cancer Center. 2013-01-18.
56. “DENdritic Cell Immunotherapy for Mesothelioma (DENIM)”. NCT03610360. Amphera BV. 2018-07-24.
57. “Mesothelioma Cancer”. Microbe Notes (2023).
58. Deng Minying., et al. “Clinical and Pathological Observation of Conversion Therapy for Malignant Peritoneal Mesothelioma: A Case Report and Literature Review”. Pathology and Oncology Research 29 (2024).
59. Kurosawa Takeyuki., et al. “Primary Malignant Pericardial Mesothelioma with Increased Serum Mesothelin Diagnosed by Surgical Pericardial Resection: A Case Report”. Molecular and Clinical Oncology5 (2016): 553-556.
60. Secil Mustafa., et al. “Imaging Features of Paratesticular Masses”. Journal of Ultrasound in Medicine7 (2017): 1487-1509.

Citation

Citation: Aravind Malireddy and Bill Tawil. “Malignant Mesothelioma: A Detailed Review of Genetic, Environmental Factors, and Therapeutic Innovations”.Acta Scientific Medical Sciences 9.4 (2025): 46-69.

Copyright

Copyright: © 2025 Aravind Malireddy and Bill Tawil. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.