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Biomolecular Pathways in Mesothelioma: What Is New Perspective on Biomolecular Research for Mesothelioma?

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Malignant Pleural Mesothelioma

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Abstract

Exposure to asbestos and to other carcinogenic fibers causes mesothelioma, an aggressive tumor with poor prognosis. Tumorigenesis originates from a chronic inflammatory process driven by high mobility group box 1 (HMGB1) and the activation of the inflammatory factors, which induce the secretion of tumor necrosis factor-α (TNF-α) and other cytokines. Over time, the chronic inflammatory process induces cell survival, favoring the accumulation of DNA mutations that activate several activated pathways, promoting tumor growth. The discovery of germline heterozygous mutations of the BRCA-associated protein 1 (BAP1) gene, conferring higher susceptibility to mesothelioma, originated from studies of gene and environment interactions. Several pathways are relevant in mesothelioma, including NF2 and Hippo, receptor tyrosine kinases like EGFR and MET, intracellular kinases such as PI3K, ERK5, and others. However, HMGB1 and BAP1 represent the most frequent and key activators of oncogenic transformation and tumor progression in mesothelioma. Therefore, the pathways activated by these two proteins, both characterized by dual activity at nuclear and cytoplasmic levels, may offer the most promising perspectives for novel therapeutic approaches to antagonize a very aggressive and refractory cancer like mesothelioma.

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Authors and Affiliations

  1. Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI, USA

    Giovanni Gaudino, Michael Minaai, Michele Carbone & Haining Yang

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  1. Giovanni Gaudino
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  2. Michael Minaai
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  3. Michele Carbone
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Correspondence to Haining Yang .

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Editors and Affiliations

  1. Center Respiratory Medicine, Otemae Hospital, Osaka, Japan

    Takashi Nakano

  2. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Takashi Kijima

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Gaudino, G., Minaai, M., Carbone, M., Yang, H. (2021). Biomolecular Pathways in Mesothelioma: What Is New Perspective on Biomolecular Research for Mesothelioma?. In: Nakano, T., Kijima, T. (eds) Malignant Pleural Mesothelioma. Respiratory Disease Series: Diagnostic Tools and Disease Managements. Springer, Singapore. https://doi.org/10.1007/978-981-15-9158-7_4

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  • DOI: https://doi.org/10.1007/978-981-15-9158-7_4

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