bims-mesote 2025-05-18 papers

Issue of 2025–05–18
three papers selected by
Laura Mannarino, Humanitas Research

Cancers (Basel). 2025 May 06. pii: 1581. [Epub ahead of print]17(9):

BAP1 Mutations and Pleural Mesothelioma: Genetic Insights, Clinical Implications, and Therapeutic Perspectives.

Susana Cedres, Augusto Valdivia, Ilaria Priano, Pedro Rocha, Patricia Iranzo, Nuria Pardo, Alex Martinez-Marti, Enriqueta Felip.

Pleural mesothelioma (PM) is a locally aggressive tumor associated with asbestos exposure. Despite legislative efforts to regulate asbestos use, its incidence continues to rise in some parts of the world. Chemotherapy and immunotherapy have improved survival in PM patients, but overall survival remains poor. Molecular analysis of PM patients has shown that most alterations occur in tumor suppressor genes, with BAP1 being the most frequently affected. Patients with germline BAP1 mutations have been reported to have a better prognosis, but this is not observed in those with somatic mutations. Interest in developing drugs targeting patients with BAP1 loss has led to several phase II studies in recent years. Unfortunately, initial results have not been very promising. In this review, we conclude that, at this time, with the contradictory results from studies and the limited number of patients evaluated, BAP1, the most commonly altered gene in PM, is not yet suitable for use in clinical practice as a prognostic or predictive factor. Future studies are needed to establish the prognostic or predictive value of BAP1.

Keywords: BAP1; biomarkers; immunotherapy; malignant pleural mesothelioma

DOI: https://doi.org/10.3390/cancers17091581

J Thorac Oncol. 2025 May;pii: S1556-0864(25)00055-3. [Epub ahead of print]20(5): e59-e60

Radical Surgery in Pleural Mesothelioma: Houston, We Have a Problem.

Jo Raskin, Jan van Meerbeeck, Paul Van Schil.

DOI: https://doi.org/10.1016/j.jtho.2025.01.022

Int J Mol Sci. 2025 May 01. pii: 4299. [Epub ahead of print]26(9):

Molecular Mechanisms of Tumor Progression and Novel Therapeutic and Diagnostic Strategies in Mesothelioma.

Taketo Kato, Ichidai Tanaka, Heng Huang, Shoji Okado, Yoshito Imamura, Yuji Nomata, Hirofumi Takenaka, Hiroki Watanabe, Yuta Kawasumi, Keita Nakanishi, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa.

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.

Keywords: BAP1; CHST4; FAK; Hippo signaling pathway; OXTR; immune checkpoint inhibitors; mesothelioma

DOI: https://doi.org/10.3390/ijms26094299