bims-mesote Biomed News
on Mesothelioma
Issue of 2025–03–02
seven papers selected by
Laura Mannarino, Humanitas Research



  1. Pharmaceutics. 2025 Feb 10. pii: 230. [Epub ahead of print]17(2):
      Background: Nitric oxide (NO) has been linked to the pathogenesis of asbestos-related pleural diseases, including an extremely aggressive cancer called malignant pleural mesothelioma (MPM). Given that MPM cells are characterized by a higher expression of NO synthases and elevated NO production relative to normal cells, the use of NO-donor compounds could potentially saturate the cancerous cells with NO, triggering their death. Methods: We developed a novel class of NO prodrugs by merging two NO-releasing components, 1,2,5-oxadiazole 2-oxides (furoxans) and 1,2,4-oxadiazoles, and studied their NO-releasing characteristics in a time-dependent manner using the Griess assay. The cytotoxicity against two human MPM cell lines and non-cancerous lung fibroblasts was evaluated using a colorimetric MTT assay. Results: All compounds exhibited excellent NO-donating properties, surpassing the capacity of two reference NO donor compounds, 3-carbamoyl-4-(hydroxymethyl)furoxan (CAS-1609) and 4-ethoxy-3-phenylsulphonylfuroxan (CHF-2363), by at least 1.5-3 times. All oxadiazole hybrids demonstrated high cytotoxicity against MPM cell lines in a low micromolar range, comparable or higher than the cytotoxicity of the standard-of-care drug cisplatin. Conclusions: Notably, the novel compounds displayed a markedly greater selectivity towards cancerous cells than cisplatin when compared with non-cancerous lung fibroblasts, aligning with the intended design.
    Keywords:  NO donors; antiproliferative activity; furoxan; malignant pleural mesothelioma; nitrogen heterocycles; oxadiazole
    DOI:  https://doi.org/10.3390/pharmaceutics17020230
  2. Commun Biol. 2025 Feb 27. 8(1): 324
      Pleural mesothelioma (PM) poses a significant challenge in oncology due to its intricate molecular and metabolic landscape, chronic inflammation, and heightened oxidative stress, which contribute to its notorious resilience and clinical complexities. Despite advancements, the precise mechanisms driving PM carcinogenesis remain elusive, impeding therapeutic progress. Here, we explore the interplay between tumor growth dynamics, lipid metabolism, and NF-κB dysregulation in malignant pleural mesothelioma, shedding light on novel molecular mechanisms underlying its pathogenesis. Our study reveals distinctive growth dynamics in PM cells, characterized by heightened proliferation, altered cell cycle progression, and resistance to apoptosis. Intriguingly, PM cells exhibit increased intracellular accumulation of myristic, palmitic, and stearic acids, suggestive of augmented lipid uptake and altered biosynthesis. Notably, we identify FABP5 as a key player in driving metabolic alterations and inflammation through NF-κB dysregulation in mesothelioma cells, distinguishing them from normal mesothelial cells. Silencing of FABP5 leads to significant alterations in cell dynamics, metabolism, and NF-κB activity, highlighting its potential as a therapeutic target. Our findings unveil a reciprocal relationship between lipid metabolism and inflammation in PM, providing a foundation for targeted therapeutic strategies. Overall, this comprehensive investigation offers insights into the intricate molecular mechanisms driving PM pathogenesis and identifies potential avenues for therapeutic intervention.
    DOI:  https://doi.org/10.1038/s42003-025-07754-0
  3. APMIS. 2025 Mar;133(3): e70006
      The 2021 WHO classification of thoracic tumours recommends grading pleural mesothelioma to aid prognostication. Robustness of grading and morphological characterisation is key to its clinical utility, though validation of this grading system has largely been conducted by expert thoracic pathologists. We conducted a survey inviting pathologists across a range of practices and expertise to grade digitised images of 50 epithelioid pleural mesotheliomas that had been graded by an expert in thoracic pathology. We included slides that were considered potentially problematic such as small biopsies, focal necrosis, and rare subtypes that may affect grading (small cell and deciduoid features). Using the Sectra Uniview web viewer, participants were asked to score atypia, mitotic count, and necrosis and choose from a list of cytological and architectural features. Seventy-four pathologists anonymously participated. There was 90% agreement of consensus scores with expert opinion using the WHO 2-tier grade and 72% for the 3-tier nuclear grade but only 70% for nuclear atypia, 56% for mitoses, and 84% for necrosis. Both 3-tier nuclear grade and WHO 2-tier grading systems were significantly associated with survival. Our study affirms the overall robustness and utility of grading for pleural mesothelioma, reveals variances, and suggests the need for dedicated training.
    Keywords:  grade; mesothelioma; prognosis; variability
    DOI:  https://doi.org/10.1111/apm.70006
  4. Epidemiol Prev. 2025 Jan-Feb;49(1):49(1): In press
       BACKGROUND: the exposure-response relationship between pleural mesothelioma and asbestos has been traditionally described by models that predicted incidence to increase indefinitely by latency. Studies with long observation showed that the increase flattens out beyond 40 years of latency. It has been, therefore, proposed to introduce an exponential decay function into the models Objectives: to show characteristics and implications as to the relevance of remote and recent exposures, by conducting a simulation exercise based on data available from the literature.
    METHODS: the traditional and decay models that best fit mortality from pleural cancer during the initial 40 years of observation in the Italian pooled cohort of asbestos workers were selected. The mesothelioma incidence predicted by such models as a function of age at first exposure, exposure duration, and age at risk was compared. It was also compared the proportional weight assigned to remote, intermediate, and recent exposure, by dividing the whole exposure period in three parts of equal duration.
    RESULTS: the decay, but not the traditional, model fits well the trend observed after 40 years. According to the traditional model, remote exposures have maximum and recent exposures minimum weight: for instance, following an exposure starting at age 20 and lasting 18 years, the incidence at age 80 would be attributed to remote exposures by 47% and by 21% to the recent ones. The decay model predicts only minor differences and even of reversed weight: 34% and 31%, respectively, in this case.
    CONCLUSIONS: remote exposures do not necessarily have overwhelming weight in determining pleural mesothelioma risk. The balance between different exposure periods depends on the time-distribution of exposure.
    Keywords:  asbestos; exposure-response relationaship; mesothelioma; time distribution of exposure
    DOI:  https://doi.org/10.19191/EP25.1.A762.002
  5. J Am Chem Soc. 2025 Feb 24.
      Although various metal-based compounds have exhibited excellent immunogenic cell death (ICD)-inducing properties both in vitro and in vivo, the majority of these compounds have been discovered serendipitously. In this work, we have successfully synthesized and characterized 35 cyclometalated Au(III) complexes containing dithiocarbamate ligands, with 25 of these complexes being previously unreported. Their ability to induce phagocytosis in vitro against immunologically "cold" malignant pleural mesothelioma (MPM) cells was strongly dependent on the cyclometalated scaffold and the overall lipophilicity of the complexes. We elucidated the role of cell death mechanisms in the observed ICD effects and identified correlations between the ability of the complexes to induce necrotic cell death and ICD, both in vitro and in vivo. Complex 2G, with its high phagocytosis rates and low necrosis rates, was recognized as a bona fide ICD inducer, demonstrating a remarkably long-lasting immune response in vaccinated mice. In contrast, complex 1C, characterized by high phagocytosis rates and high necrosis rates, failed to elicit a sustained immune response upon following vaccination; however, it triggered selective activation of calreticulin in tumors upon direct in vivo administration. Overall, this study offers a framework for predicting ICD effects in vivo for structurally similar Au(III) complexes, with the potential for extension to other series of metal complexes.
    DOI:  https://doi.org/10.1021/jacs.4c17966
  6. Future Oncol. 2025 Feb 25. 1-12
      In recent years, the thoracic malignancies treatment landscape has become more complex with the emergence of novel targeted and immunotherapy-based treatments. Although beneficial to patients and physicians, this fast-paced therapeutic evolution has increased the complexity of clinical decision-making and amplified the importance of real-world evidence to support data from randomized controlled trials. The international I-O Optimise initiative was established in 2016 to provide real-world insights into the thoracic malignancies treatment landscape, and has since collaborated with 14 data sources across Europe and Canada, allowing access to data from ~ 500,000 patients with non-small-cell lung cancer, small-cell lung cancer, and malignant pleural mesothelioma. This article reviews pertinent I-O Optimise research, with discussion of the methodological/data-related learnings and expectations for future insights.
    Keywords:  Database; lung cancers; mesothelioma; non-small-cell lung cancer; real-world evidence; small-cell lung cancer; survival; thoracic malignancies
    DOI:  https://doi.org/10.1080/14796694.2025.2466416
  7. Cancers (Basel). 2025 Feb 18. pii: 694. [Epub ahead of print]17(4):
      Mesothelioma is a highly malignant condition arising from the pleura and peritoneum that is closely related to asbestos exposure. The prognosis for this condition has traditionally been poor due to the difficulty physicians have faced in diagnosing and treating this disease, even in its early phase. Fortunately, recent advances in both the molecular understanding of the development of this disease and innovative and novel treatment modalities have accelerated the discovery of new ways to treat mesothelioma. In this review, we first summarize the mechanism of mesothelioma pathophysiology and then relate it to emerging treatment modalities. These include immunotherapy or immune checkpoint inhibitors (ICIs), molecular targeted therapies, and cell-based therapies (such as CAR-T cells or dendritic cells). The scientific basis for the utilization of these treatment modalities, alongside the current clinical evidence for each option, will be explored in detail later on. The hope is that this review can elucidate how these emerging therapeutic options work clinically to help accelerate further developments in novel mesothelioma treatment modalities.
    Keywords:  CAR-T cells; dendritic cells; immune checkpoint inhibitors; immunotherapy; mesothelioma; molecular targeted therapy
    DOI:  https://doi.org/10.3390/cancers17040694