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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Mesothelioma is characterized by the inactivation of tumor suppressor genes, with frequent mutations in neurofibromin 2 (NF2), BRCA1-associated protein 1 (BAP1), and cyclin-dependent kinase inhibitor 2A (CDKN2A). These mutations lead to disruptions in the Hippo signaling pathway and histone methylation, thereby promoting tumor growth. NF2 mutations result in Merlin deficiency, leading to uncontrolled cell proliferation, whereas BAP1 mutations impair chromatin remodeling and hinder DNA damage repair. Emerging molecular targets in mesothelioma include mesothelin (MSLN), oxytocin receptor (OXTR), protein arginine methyltransferase (PRMT5), and carbohydrate sulfotransferase 4 (CHST4). MSLN-based therapies, such as antibody–drug conjugates and immunotoxins, have shown efficacy in clinical trials. OXTR, upregulated in mesothelioma, is correlated with poor prognosis and represents a novel therapeutic target. PRMT5 inhibition is being explored in tumors with MTAP deletions, commonly co-occurring with CDKN2A loss. CHST4 expression is associated with improved prognosis, potentially influencing tumor immunity. Immune checkpoint inhibitors targeting PD-1/PD-L1 have shown promise in some cases; however, resistance mechanisms remain a challenge. Advances in multi-omics approaches have improved our understanding of mesothelioma pathogenesis. Future research will aim to identify novel therapeutic targets and personalized treatment strategies, particularly in the context of epigenetic therapy and combination immunotherapy.

Details

Title
Molecular Mechanisms of Tumor Progression and Novel Therapeutic and Diagnostic Strategies in Mesothelioma
Author
Kato Taketo 1   VIAFID ORCID Logo  ; Tanaka Ichidai 2 ; Huang, Heng 1 ; Okado Shoji 1 ; Imamura Yoshito 1 ; Nomata Yuji 1 ; Takenaka Hirofumi 1 ; Watanabe, Hiroki 1 ; Kawasumi Yuta 1 ; Nakanishi Keita 1 ; Kadomatsu Yuka 1 ; Ueno Harushi 1   VIAFID ORCID Logo  ; Nakamura Shota 1   VIAFID ORCID Logo  ; Mizuno Tetsuya 1 ; Chen-Yoshikawa Toyofumi Fengshi 1   VIAFID ORCID Logo 

 Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; [email protected] (T.K.); [email protected] (H.H.); [email protected] (S.O.); [email protected] (Y.I.); [email protected] (Y.N.); [email protected] (H.T.); [email protected] (H.W.); [email protected] (Y.K.); [email protected] (K.N.); [email protected] (Y.K.); [email protected] (H.U.); [email protected] (S.N.); [email protected] (T.M.) 
 Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; [email protected] 
First page
4299
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3203203526
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.