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

• Published in: International journal of molecular sciences 2018-01, Vol.19 (1), p.238
• Main Authors: Tolani, Bhairavi, Acevedo, Luis A, Hoang, Ngoc T, He, Biao
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Angiogenesis; Apoptosis; Asbestos; Cancer therapies; Carcinogenesis; Carcinogens; Cell cycle; Chemotherapy; Clinical trials; developmental cell pathways; Disease Progression; Drug development; FDA approval; Genes, Tumor Suppressor; Genome; Growth factors; Humans; Immune system; Immunology; immunotherapy; Kinases; Ligands; Liver cancer; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; malignant pleural mesothelioma (MPM); Medical prognosis; Mesothelioma; Mesothelioma - genetics; Mesothelioma - immunology; Mesothelioma - pathology; Mesothelioma, Malignant; molecular pathways; Multiple myeloma; Mutation; Patients; Pleural Neoplasms - genetics; Pleural Neoplasms - immunology; Pleural Neoplasms - pathology; Radiation; Review; Thyroid gland; Tumor Microenvironment; tumor microenvironment heterogeneity; Tumor suppressor genes; tumor suppressors; Tumors; Typing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19010238

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 ; and . 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.