bims-mesote Biomed News
on Mesothelioma
Issue of 2026–02–15
seven papers selected by
Laura Mannarino, Humanitas Research



  1. Respir Med Res. 2025 Nov 28. pii: S2590-0412(25)00078-9. [Epub ahead of print]89 101231
       BACKGROUND: The diagnosis of malignant pleural mesothelioma (MPM) can be challenging for clinicians and pathologists.
    PATIENTS AND METHODS: This study included all patients diagnosed with pleural mesothelioma between October 2013 and April 2024. Clinical data, history of asbestos exposure, pleural fluid analysis, chest-X-ray, thoracic computed tomography and positron emission tomography findings, video-assisted thoracic surgery report, pleural fluid cytology and pleural biopsy results were included. Loss of BRCA1-associated protein 1 (BAP1) nuclear staining was examined in cytologies and biopsies.
    RESULTS: Forty-one patients were diagnosed with pleural mesothelioma, 35 epithelioid, 5 sarcomatoid and 1 biphasic. The diagnosis was established after the first sample in 30 patients, while a second one was necessary in 11 patients. BAP1 loss in pleural cytology and histology was not always consistent. Sixteen patients showed loss of BAP1 expression in cytology. Among these, 10 patients also presented BAP1 loss in pleural histology, whereas 5 patients with BAP1 loss in histology did not show BAP1 loss in cytology. Additionally, two patients initially diagnosed with idiopathic pleural effusion and 3 patients diagnosed with benign pleural effusion due to asbestos showed BAP1 loss and were later diagnosed with MPM during follow-up.
    CONCLUSION: MPM remains difficult to diagnose. Performing BAP1 immunohistochemistry in patients with an undiagnosed pleural effusion or a history of asbestos exposure can aid in identifying those with mesothelioma.
    Keywords:  BAP1; Mesothelioma; Pleural effusion
    DOI:  https://doi.org/10.1016/j.resmer.2025.101231
  2. Cancers (Basel). 2026 Jan 27. pii: 405. [Epub ahead of print]18(3):
       BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm, the major cause of which is asbestos exposure. Adjuvant radiotherapy after pleurectomy/decortication (P/D) aims at reducing locoregional recurrence but is limited by the risk of radiation pneumonitis (RP). In this study, we attempted to evaluate the predictive value of conventional and functional dosimetric parameters in assessing RP risk.
    METHODS: This retrospective study analyzed 68 patients with non-metastatic MPM treated with adjuvant radiotherapy after P/D. Dosimetric parameters, including V20, V5, and mean lung dose (MLD), were calculated for both total lung volume and functional lung volume (FLV), with emphysematous regions excluded based on CT imaging thresholds. Statistical analyses assessed correlations between these parameters and acute RP incidence.
    RESULTS: Acute RP developed in 42% of patients, and 28% had moderate-to-severe (Grade 2-3) events. V20 and FCL_V20 were significantly associated with the risk of RP (p = 0.017 and p = 0.028, respectively). Predictive accuracy for conventional V20 (AUC = 0.668) and Functional Contralateral Lung V20 (FCL_V20) (AUC = 0.655) showed moderate efficacy, without further significant improvement in using functional parameters. A V20 threshold > 1.8% predicted severe RP with high specificity (89.8%).
    CONCLUSIONS: While functional lung delineation provides an alternative in dosimetry, conventional V20 is a robust predictor of RP. Optimization of dosimetric constraints, in an effort to reduce pulmonary toxicity in MPM patients, should be further combined with advanced radiotherapy techniques and biomarkers.
    Keywords:  IMRT; V20; biomarkers; dosimetric parameters; functional lung volume; malignant pleural mesothelioma; radiation pneumonitis; radiotherapy toxicity
    DOI:  https://doi.org/10.3390/cancers18030405
  3. Cancers (Basel). 2026 Jan 26. pii: 381. [Epub ahead of print]18(3):
      Background/Objectives: Pleural mesothelioma (PM) frequently recurs despite multimodal therapy. Here, we aimed to retrospectively evaluate the safety and potential clinical benefit of radiofrequency ablation (RFA) for recurrent PM. Methods: Fourteen consecutive patients underwent CT-guided RFA between July 2019 and June 2025. The cohort comprised 13 men and 1 woman, with a median age of 69 (range, 54-77) years. All patients had previously received systemic therapy, and 12 had undergone surgery. Seven patients (50%) presented with multiple lesions, and 25 tumors (median diameter 1.8 cm; range, 0.5-7.0 cm) were treated in 23 sessions. Outcomes assessed were local tumor control, complications, and survival. Local progression and overall survival were estimated using Kaplan-Meier analysis. Adverse events were classified according to the Society of Interventional Radiology guidelines. Results: Technical success was achieved in all sessions. Two tumors showed local recurrence, corresponding to 1- and 2-year local progression rates of 10.6%. Seven patients showed distant metastases, most of whom subsequently received systemic therapy. Three patients died, two from disease progression and one from treatment-related gastrointestinal perforation during therapy for an unrelated cancer. The overall survival rates were 100%, 100%, and 60% at 1, 3, and 5 years, respectively. Major and minor complications occurred in one case each (4.3%): a refractory skin ulcer and retroperitoneal hematoma, respectively. Conclusions: RFA was technically feasible and generally well tolerated and helped achieve encouraging local control and survival in patients with recurrent PM, warranting further evaluation of RFA as a complementary approach in multimodal treatment strategies.
    Keywords:  clinical outcomes; pleural mesothelioma; radiofrequency ablation; safety; survival
    DOI:  https://doi.org/10.3390/cancers18030381
  4. Transl Lung Cancer Res. 2026 Jan 31. 15(1): 11
       Background: Pleural mesothelioma (PM) represents an uncommon and exceptionally lethal malignancy. The sarcomatoid subtype constitutes the rarest histological variant, traditionally linked to the worst prognosis, while the advantages of operative intervention remain inadequately established. In this study, we present findings from a cohort of 34 sequential cases with sarcomatoid mesothelioma managed at a specialized high-volume center employing pleurectomy decortication (PD) within a comprehensive therapeutic strategy. We aim to identify patients in this cohort who may benefit from a multimodality approach.
    Methods: All patients diagnosed with sarcomatoid mesothelioma between 2007 and 2019 who received PD at our facility were enrolled, and relevant medical, histopathological, and operative data collected. Survival curves generated through Kaplan-Meier methodology alongside log-rank testing enabled comparison of longevity outcomes, while Cox proportional hazards modeling facilitated examination of predictive variables.
    Results: The cohort included 31 male subjects (91.2%), 24 procedures performed on the right side (70.6%), with a median patient age of 71.5 years (range, 51-85 years). Preoperative treatment was administered to 8 individuals (24.2%), while 23 participants (67.7%) underwent intraoperative heated chemotherapy (IOHC). Macroscopic complete resection (MCR) was accomplished in 22 cases (64.7%). Mortality at 30 and 90 days post-surgery stood at 2.9% and 14.7%, respectively. The median overall survival for the entire cohort reached 7.4 months, extending to 20.1 months among those with forced expiratory volume in 1 second (FEV1) at or above 80% predicted. In multivariate analysis, preoperative FEV1 ≥80% was associated with prolonged overall survival [P=0.01; hazard ratio (HR) =0.54].
    Conclusions: As expected, the median survival for most patients with sarcomatoid histology who undergo surgery is under one year. However, a small subset of patients with FEV1 ≥80% do quite well using the multimodality approach.
    Keywords:  Pleural mesothelioma (PM); forced expiratory volume in 1 second (FEV1); macroscopic complete resection (MCR); pleurectomy decortication (PD); sarcomatoid mesothelioma
    DOI:  https://doi.org/10.21037/tlcr-2025-990
  5. Sci Rep. 2026 Feb 11.
      Pleural mesothelioma (PM) is a highly aggressive cancer with limited treatment efficacy and poor prognosis. Conventional two-dimensional (2D) culture models fail to replicate the tumour microenvironment (TME), limiting their translational relevance. Here, we establish a three-dimensional (3D) spheroid model to investigate chemotherapy resistance across different PM subtypes. Compared to 2D cultures, 3D spheroids display enhanced resistance to cisplatin-pemetrexed, with elevated IC₅₀ values, reduced apoptosis, and altered cell cycle profiles. Seahorse metabolic analysis of 3D spheroids demonstrate a suppressed metabolic phenotype, characterised by reduced oxidative phosphorylation (OCR). However, the glycolytic capacity was not upregulated, consistent with the hypoxic and nutrient-limited conditions observed in mesothelioma lesions. In parallel, molecular profiling identifies subtype-specific miRNA signatures that closely align with patient-derived datasets. Proteomic analysis of 3D cultures identifies upregulation of PI3K/AKT and Notch/VEGF signalling, implicating these pathways in treatment resistance. Histological assessment of xenografts further confirms 3D model fidelity in capturing tumour fibrosis, necrosis, and response to therapy. These findings position the 3D spheroid system as a robust and physiologically relevant platform for modelling drug resistance and guiding therapeutic development in PM.
    DOI:  https://doi.org/10.1038/s41598-026-38692-4
  6. Cells. 2026 Feb 02. pii: 283. [Epub ahead of print]15(3):
      SATB2 (special AT-rich binding protein 2) functions as a chromatin-associated epigenetic regulator that modulates gene expression, in part by serving as a transcriptional cofactor. This study assessed whether SATB2 overexpression is sufficient to promote in vitro transformation of human mesothelial cells and whether SATB2 suppression in mesothelioma cancer stem cell (CSC)-enriched populations is associated with altered chemoresistance. SATB2 expression was high in human malignant pleural mesothelioma (MPM) cell lines but absent in Met5A mesothelial cells. Ectopic SATB2 expression in Met5A cells was associated with acquisition of malignant and stem cell-like phenotypes, including increased expression of stem cell markers and pluripotency-associated factors, as well as anchorage-independent growth in soft agar and spheroid formation in suspension culture. In contrast, Met5A cells transduced with an empty vector did not form colonies or mesospheres. SATB2 overexpression in Met5A cells was also associated with increased motility, migration, and invasion, accompanied by induction of epithelial-mesenchymal transition (EMT)-related transcription factors relative to empty vector controls. Conversely, shRNA-mediated SATB2 knockdown in an MPM cell line attenuated proliferation, EMT-associated features, and CSC-like characteristics. Chromatin immunoprecipitation assays identified SATB2 occupancy at promoter regions of Bcl2, XIAP, KLF4, c-Myc, NANOG, and SOX2, consistent with a role in transcriptional regulation of genes linked to transformation, pluripotency, cell survival, proliferation, and EMT. In CSC-enriched cells, SATB2 inhibition was associated with increased sensitivity to cisplatin and pemetrexed, concomitant with reduced OCT4 and SOX2 expression. Collectively, these findings support SATB2 as a candidate therapeutic target in MPM and suggest that SATB2 suppression may enhance chemotherapy response when combined with standard agents.
    Keywords:  Nanog; SATB2; apoptosis; cancer stem cells; drug resistance; epithelial–mesenchymal transition; mesothelioma; spheroids; transformation
    DOI:  https://doi.org/10.3390/cells15030283