bims-mesote 2025-05-25 papers

Issue of 2025–05–25
five papers selected by
Laura Mannarino, Humanitas Research

J Thorac Dis. 2025 Apr 30. 17(4): 2014-2027

A bibliometric analysis of malignant pleural mesothelioma from 2010 to 2023.

Sheng Chen, Ce Zhao, Ruiqi Liu, Wenjie Jiao.

Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor originating from the mesothelial lining of the pleural cavity. It is characterized by extensive nodular pleural thickening and has a propensity to invade the pleural adipose tissue and adjacent chest structures. The prognosis is poor, with a median survival time rarely exceeding 12 months following diagnosis.
Methods: This bibliometric analysis systematically assessed global trends in MPM research from 2010 to 2023 using 6,487 publications indexed in PubMed. Quantitative evaluations of publication metrics, international collaboration, and keyword co-occurrence networks were conducted using R software with the bibliometrix package. Network construction and thematic mapping were employed to analyze the temporal evolution of research topics.
Results: The United States and Europe have played pivotal roles in this research, while contributions from China and Japan have been steadily increasing. Traditional treatment approaches and etiological studies are relatively well-established. Meanwhile, immunotherapy has emerged as a prominent focus of recent research.
Conclusions: Future global collaboration in this field should be enhanced, as precision medicine related to immunology and genetics has the potential to transform the treatment landscape of MPM.

Keywords: Bibliometrics; immunotherapy; malignant pleural mesothelioma (MPM)

DOI: https://doi.org/10.21037/jtd-24-1778

Cancer Sci. 2025 May 23.

KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin-Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma.

Takashi Kijima, Terufumi Kato, Yasushi Goto, Kozo Kuribayashi, Koji Mikami, Yoshiki Negi, Shuji Murakami, Tatsuya Yoshida, Masae Homma, Akira Wakana, Kazuo Noguchi, Nobukazu Fujimoto.

Pleural mesothelioma (PM) is an inflammatory cancer linked with asbestos exposure and has a poor prognosis. We report results of the phase 1b KEYNOTE-A17 study (NCT04153565) of first-line pembrolizumab plus chemotherapy in Japanese participants with advanced PM. Participants aged ≥ 20 years with previously untreated, histologically confirmed advanced or unresectable PM received pembrolizumab 200 mg every 3 weeks (Q3W) for ≤ 35 cycles with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 Q3W for 4-6 cycles. Primary endpoints were the rate of dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. DLTs were assessed during cycle 1 in 18 participants, and having ≤ 8 participants with DLTs was considered tolerable. AEs were graded per NCI CTCAE 5.0. Tumor response was evaluated per modified RECIST for PM by the investigator. Among 19 participants enrolled, the median study follow-up was 30.8 (range, 27.8-33.3) months (data cutoff September 21, 2022). Of 18 participants evaluated for DLTs, 2 (11%) experienced 4 DLTs (hypoalbuminemia, malaise, pyrexia in 1 participant; uveitis in 1 participant). 18/19 participants (95%) experienced treatment-related AEs; 14 (74%) had grade 3-4 events (no grade 5). Treatment-related AEs led to discontinuation of any drug in 5 participants (26%). The objective response rate was 74% (partial response, n = 14), and the median (range) duration of response was 16.8 (3.0-26.3+) months. First-line pembrolizumab plus chemotherapy was tolerable based on the low incidence of DLTs and showed acceptable safety and preliminary antitumor activity in Japanese participants with advanced PM. Trial Registration: NCT04153565.

Keywords: Japan; cisplatin; pembrolizumab; pemetrexed; pleural mesothelioma

DOI: https://doi.org/10.1111/cas.70082

Exp Mol Pathol. 2025 May 20. pii: S0014-4800(25)00023-1. [Epub ahead of print]143 104973

From asbestos exposure to carcinogenesis: Transcriptomic signatures in malignant pleural mesothelioma.

Diletta Rosati, Bianca Giulia Maurizi, Viola Bianca Serio, Debora Maffeo, Angela Rina, Francesca Mari, Maria Palmieri, Antonio Giordano, Elisa Frullanti.

BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) has surged due to widespread asbestos exposure, particularly since the mid-20th century. Despite significant advancements in cancer treatment, an effective cure for MPM remains elusive, largely due to a limited understanding of the molecular mechanisms underlying asbestos-related carcinogenesis. This exploratory study aims to uncover gene expression patterns uniquely altered in mesothelioma patients with documented asbestos exposure, providing a solid foundation for future research focused on identifying novel prognostic and predictive biomarkers.
METHODS: Publicly available RNA sequencing data were analyzed through a bioinformatics pipeline to perform differential gene expression analysis. Additionally, functional enrichment analysis was applied to highlight significantly enriched Gene Ontology (GO) terms related to biological processes, molecular functions, and cellular components, offering insights into the molecular pathways involved in MPM development.
RESULTS: The analysis uncovered a set of differentially expressed genes (DEGs) in MPM patients with documented asbestos exposure, as well as key GO terms. These enriched biological terms reflect processes such as ion homeostasis and oxidative stress response, providing crucial information on the cellular alterations driven by asbestos exposure.
CONCLUSION: This study's findings deepen our understanding of the molecular landscape underlying asbestos-induced carcinogenesis in MPM. The identification of specific DEGs and enriched GO terms lays the foundation for future investigations, including the development of biomarkers, with potential implications for the diagnostic and prognostic assessment of MPM.

Keywords: Asbestos exposure; Biomarkers; Differentially expressed genes (DEGs); Malignant pleural mesothelioma (MPM); Oxidative stress

DOI: https://doi.org/10.1016/j.yexmp.2025.104973

Clin Lung Cancer. 2025 Apr 22. pii: S1525-7304(25)00079-8. [Epub ahead of print]

Breaking Through: Immunotherapy Innovations in Pleural Mesothelioma.

Amalia A Sofianidi, Nikolaos K Syrigos, Kevin G Blyth, Andriani Charpidou, Ioannis A Vathiotis.

The prognosis of pleural mesothelioma (PM) is poor and conventional chemotherapy regimens have shown limited antitumor activity. Recent use of immune checkpoint inhibitors (ICIs) has shown promise, with CheckMate-743 trial establishing nivolumab plus ipilimumab as first line treatment in unresectable PM. Nevertheless, real-world applicability as well as differential benefit of immunotherapy according to histologic are areas of active debate. In addition, increased incidence of immune-related adverse events (IRAEs) and high discontinuation rates highlight the need for careful patient selection. While ICIs represent a significant advancement in PM treatment, ongoing research is necessary to refine their use, potentially through biomarker-informed approaches, and manage associated toxicities. This review highlights the evolving landscape of immunotherapy and associated controversies in PM.

Keywords: Biomarkers; Controversies; Immune checkpoint inhibitors (ICIs)

DOI: https://doi.org/10.1016/j.cllc.2025.04.008

Phytomedicine. 2025 May 06. pii: S0944-7113(25)00424-6. [Epub ahead of print]143 156786

Deoxypodophyllotoxin inhibited the growth of malignant pleural mesothelioma by inducing necroptosis and mitotic catastrophe.

Cheng Zhong, Shenqi Wang, Jingyuan Zhang, Qi Zheng, Yuqiong Lei, Yongle Xu, Tao Ren, Rong Sun.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an extremely aggressive cancer with a poor prognosis and limited effective treatment options. However, recent studies have shown that targeting microtubule regulation is a viable approach for treating MPM.
PURPOSE: This study aimed to assess the antitumor behavior of deoxypodophyllotoxin (DPT) on MPM in vitro and in vivo and to identify its underlying mechanisms.
STUDY DESIGN: The study employed in vitro and in vivo models to evaluate the efficacy and mechanisms of DPT against MPM. We used cell-culture techniques, molecular-biology assays, and a xenograft mice module to thoroughly study the effects of DPT.
METHODS: Three MPM cell lines (H2452, H28, and 211H) and a xenograft mice module were used to assess the antitumor effects of DPT. The cell-cycle and cell-death rates were assessed by flow cytometry to study DPT-induced mitotic cell death. Moreover, the role of necroptosis in the antitumor effect of DPT was determined through transmission electron microscopy and western blot analysis, with further validation being done via RIP1 inhibition by Necrostatin-1 (Nec-1), a RIPK1 inhibitor, and MLKL silencing by siRNAs.
RESULTS: DPT was found to inhibit MPM cell growth in a dose-dependent manner in vitro and in vivo. Specifically, transmission electron microscopy showed plasma-membrane rupture with the preserved nuclear integrity of MPM cells after DPT treatment, indicating necroptosis in DPT-treated MPM cells. Moreover, a western blot revealed further proof of tumor necrosis factor alpha (TNF-α)-associated necroptosis-pathway activation, as revealed by the phosphorylation of the key proteins receptor-interacting protein kinase 1 (RIP1), receptor-interacting protein kinase 3 (RIP3), and mixed-lineage kinase domain-like pseudokinase (MLKL). Additional experiments with TNF-α receptor TNFR1 silencing, RIP1 inhibitors and MLKL silencing reinforced the influential role of TNF-α- RIP1-RIP3-MLKL activation in DPT-induced necroptosis. Also, DPT triggered mitotic catastrophe, observable by a defective spindle assembly, multinucleation, and micronucleation. Pretreatment with the S-phase arrest inducer thymidine was reduced both DPT-induced cell death and RIP1 phosphorylation, suggesting an interplay between necroptosis and mitotic arrest.
CONCLUSION: DPT may offer a novel therapeutic option for MPM, with drug-induced necroptosis and mitotic catastrophe being key underlying mechanisms.

Keywords: Deoxypodophyllotoxin; Malignant pleural mesothelioma; Mitotic catastrophe; Necroptosis

DOI: https://doi.org/10.1016/j.phymed.2025.156786