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Int. J. Mol. Sci. 2018, 19(1), 238; https://doi.org/10.3390/ijms19010238

Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications

Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA
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Received: 21 November 2017 / Revised: 8 January 2018 / Accepted: 10 January 2018 / Published: 13 January 2018
(This article belongs to the Special Issue Mesothelioma Heterogeneity: Potential Mechanisms)
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Abstract

Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5–12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure. Several molecular pathways have been implicated in the MPM tumor microenvironment; such as angiogenesis; apoptosis; cell-cycle regulation and several growth factor-related pathways predicted to be amenable to therapeutic intervention. Furthermore, the availability of genomic data has improved our understanding of the pathobiology of MPM. The MPM genomic landscape is dominated by inactivating mutations in several tumor suppressor genes; such as CDKN2A; BAP1 and NF2. Given the complex heterogeneity of the tumor microenvironment in MPM; a better understanding of the interplay between stromal; endothelial and immune cells at the molecular level is required; to chaperone the development of improved personalized therapeutics. Many recent advances at the molecular level have been reported and several exciting new treatment options are under investigation. Here; we review the challenges and the most up-to-date biological advances in MPM pertaining to the molecular pathways implicated; progress at the genomic level; immunological progression of this fatal disease; and its link with developmental cell pathways; with an emphasis on prognostic and therapeutic treatment strategies. View Full-Text
Keywords: malignant pleural mesothelioma (MPM); tumor microenvironment heterogeneity; molecular pathways; tumor suppressors; immunotherapy; developmental cell pathways malignant pleural mesothelioma (MPM); tumor microenvironment heterogeneity; molecular pathways; tumor suppressors; immunotherapy; developmental cell pathways
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Tolani, B.; Acevedo, L.A.; Hoang, N.T.; He, B. Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications. Int. J. Mol. Sci. 2018, 19, 238.

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