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22.05.2019 | Review Article

The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment

verfasst von: Vasiliki Galani, Anna Varouktsi, Stamatis S. Papadatos, Antigoni Mitselou, Ioannis Sainis, Stavros Constantopoulos, Yotanna Dalavanga

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2019

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Abstract

Malignant mesothelioma (MM) is a highly aggressive tumor that is strongly related to asbestos fiber exposure. The tumorigenesis procedure in MM is complex, and many pathogenetic mechanisms including chronic inflammation, deregulation of cell death, and the genomic copy-number losses and gains may contribute to carcinogenesis. MM cells are resistant to TRAIL-mediated apoptosis due to defects in extrinsic apoptotic pathway. CAPS, a regulator of cell cycle and death, may contribute to the MM development as well. BAP1 is the most frequently inactivated gene in MPM; BAP1 deficiency triggers malignant transformation via disruption of DNA repair, transcription regulation, cell metabolism, apoptosis, and ferroptosis. In addition, bcl-2 family proteins as well as abnormal activation of PI3 K/Akt/mTOR pathway and deregulation of the Wnt signaling pathway may result in MM tumorigenesis. Finally, the Hippo pathway plays a critical role in MPM development. Mutations of NF2 and LATS lead to YAP activation in MPM. Thus, inhibition of YAP activity by YAP inhibitors could be a potentially promising treatment option for MM. In conclusion, extensive genetic alterations exist in mesotheliomas associated with the signaling of apoptotic HM cells death. The comprehension of these pathways may contribute to enhancing survival via developing new effective therapeutic strategies.

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Titel: The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment
verfasst von: Vasiliki Galani
Anna Varouktsi
Stamatis S. Papadatos
Antigoni Mitselou
Ioannis Sainis
Stavros Constantopoulos
Yotanna Dalavanga
Publikationsdatum: 22.05.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03878-3

Springer Medizin

The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment

Abstract

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