bims-mesote Biomed News
on Mesothelioma
Issue of 2026–02–01
eight papers selected by
Laura Mannarino, Humanitas Research
  1. PD-L1 and BAP1 as Prognostic Biomarkers in Malignant Pleural Mesothelioma.
  2. Mechanisms of Chemoresistance in Malignant Pleural Mesothelioma: The Regulatory Role of miRNAs.
  3. An Autopsy Case of Pleural Mesothelioma Progressed Rapidly With Multiple Organ Metastases During Immune Checkpoint Inhibitor Therapy.
  4. Reactive Oxygen Species Drive Cell Migration and PD-L1 Expression via YB-1 Phosphorylation in Pleural Mesothelioma.
  5. Spatio-temporal trends in pleural mesothelioma mortality in Italy: a 40-year analysis by calendar period and birth cohort.
  6. Treatment Patterns, Clinical Outcomes, Health Care Resource Use, and Costs in Older Adults with Malignant Pleural Mesothelioma in the United States, 2007-2020.
  7. Pembrolizumab Plus Platinum Doublet Chemotherapy With Lenvatinib in Unresectable Pleural Mesothelioma as First-Line Treatment (PENINSULA): A Study Protocol for a Single-Arm, Multi-Institutional, Phase II Clinical Trial.
  8. The Diagnostic Trap in Radiation-Induced Mesothelioma: Kinetic-Morphological Decoupling Masks Molecular Aggression.
  1. Cells. 2026 Jan 19. pii: 183. [Epub ahead of print]15(2):
    PD-L1 and BAP1 as Prognostic Biomarkers in Malignant Pleural Mesothelioma.
    Milija Gajić, Vesna Ćeriman Krstić, Natalija Samardžić, Ivan Soldatović, Sofija Glumac, Milena Jovanović, Milan Savić, Mihailo Stjepanović, Spasoje Popević, Ruža Stević, Nikola Čolić, Katarina Lukić, Vladimir Milenković, Ivan Milivojević, Ivana Sekulović Radovanović, Dragana Jovanović.
      Malignant pleural mesothelioma (MPM) is a very aggressive tumor. The prognostic value of PD-L1 and BAP1 expression has been investigated in many studies. A retrospective study was conducted that analyzed PD-L1 and BAP1 expression as prognostic biomarkers in patients with MPM. The study included 53 patients with MPM. PD-L1 expression ≥ 1% was found in 39.6%, and BAP1 loss was found in 81.1% of patients. The median overall survival (mOS) was 11 months. Subtype of MPM (p = 0.045), early tumor stage (p = 0.049), therapy (p = 0.002), and good PS (0-1) (p = 0.012) were associated with better survival. Expression of PD-L1 and BAP1 did not show statistical significance regarding OS, but OS was numerically shorter in patients with PD-L1 ≥ 10% (5 vs. 12 months) and longer in patients with BAP1 loss (12 vs. 4 months). In patients with PD-L1 ≥ 1% and BAP1 loss, the median progression-free survival (mPFS) was numerically longer (10 vs. 7 months) but in patients with PD-L1 ≥ 1% and BAP1 positivity, PFS was statistically significantly shorter (1 vs. 7 months, p = 0.048). Our results did not show that PD-L1 and BAP1 are prognostic biomarkers for MPM, but positive PD-L1 expression and BAP1 loss were associated with worse survival in patients with MPM.
    Keywords:  BAP1; PD-L1; malignant pleural mesothelioma; prognostic biomarker
    DOI:  https://doi.org/10.3390/cells15020183
  2. Arch Med Res. 2026 Jan 27. pii: S0188-4409(25)00146-8. [Epub ahead of print]57(4): 103326
    Mechanisms of Chemoresistance in Malignant Pleural Mesothelioma: The Regulatory Role of miRNAs.
    Andrea Martinez-Marroquin, Javier Gaytán-Cervantes, Haydeé Rosas-Vargas, Constantino López-Macías, Itzel Peralta-Salguero, Miguel Cid-Soto, Violeta Castro Leyva, Marlon De Ita, Carolina González-Torres.
      Malignant pleural mesothelioma (MPM), is a rare and aggressive cancer that originates in the mesothelium lining the lungs. It is considered an occupational disease associated with exposure to asbestos in the workplace. MPM is often diagnosed in the late stages and has a poor response to treatment. Since the cause of the limited response to therapy in patients with MPM is unknown, it is necessary to establish the mechanisms related to chemoresistance, such as microRNAs (miRNAs), which play a specific role. Several studies have demonstrated that the downregulation of miR-15 and miR-16 in MPM cell lines is associated with chemoresistance, and that their overexpression contributes to sensitizing cells to chemotherapy. In addition, some miRNAs have been shown to be associated with epithelial-mesenchymal transition (EMT) in MPM cells. EMT has been linked to the acquisition of a chemoresistant phenotype; moreover, the release of miRNAs into circulating exosomes from patients with MPM could also impact the resistance to conventional treatments. This review aims to summarize the current knowledge on the role of miRNAs in MPM and their relationship with chemoresistance, as well as to establish new knowledge to support the development of improved treatment for patients with MPM.
    Keywords:  Cancer; Chemoresistance; Epithelial- mesenchymal transition; Exosomes; Malignant pleural mesothelioma; Mirnas
    DOI:  https://doi.org/10.1016/j.arcmed.2025.103326
  3. Pathol Int. 2026 Jan;76(1): e70088
    An Autopsy Case of Pleural Mesothelioma Progressed Rapidly With Multiple Organ Metastases During Immune Checkpoint Inhibitor Therapy.
    Mihoko Yamamoto-Rikitake, Takeshi Yamaryo, Kazuki Nabeshima, Toshiaki Yoshida.
      Immune checkpoint inhibitors (ICIs) were approved in Japan in 2021 for the initial treatment of pleural mesothelioma (PM), offering anticipated prognostic benefits. However, reports of atypical responses exist. We report the case of an 80-year-old man with PM who, despite primary tumor shrinkage on ICI treatment, died of small intestinal perforation resulting from rapid, multiorgan metastasis. This case provided an opportunity to examine the histological changes in PM post-ICI treatment. The rapid clinical course was suggestive of hyperprogressive disease (HPD), a pattern of unexpectedly accelerated progression. Atypical response patterns remain rare in PM, and it is noteworthy that in this case fulminant metastatic progression occurred concurrently with marked regression of the primary pleural lesion. We believe this is a significant case worthy of presentation.
    Keywords:  autopsy; hyperprogressive disease; immune checkpoint inhibitor; metastasis; pleural mesothelioma
    DOI:  https://doi.org/10.1111/pin.70088
  4. Antioxidants (Basel). 2026 Jan 17. pii: 121. [Epub ahead of print]15(1):
    Reactive Oxygen Species Drive Cell Migration and PD-L1 Expression via YB-1 Phosphorylation in Pleural Mesothelioma.
    Muhammad Hashim, Gerald Timelthaler, Dominik Kirchhofer, Beatrice Irina Kudlacek, Berta Mosleh, Katharina Sinn, Ezzat Mohamed Awad, Mir Alireza Hoda, Bettina Grasl-Kraupp, Balazs Dome, Walter Berger, Georg Krupitza, Karin Schelch, Michael Grusch.
      Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.
    Keywords:  ROS; cell migration; cell signalling; immune checkpoint proteins; pleural mesothelioma
    DOI:  https://doi.org/10.3390/antiox15010121
  5. Int J Epidemiol. 2026 Jan 02. pii: dyaf227. [Epub ahead of print]55(1):
    Spatio-temporal trends in pleural mesothelioma mortality in Italy: a 40-year analysis by calendar period and birth cohort.
    Allegra Sartore, Giorgia Stoppa, Giada Minelli, Lucia Fazzo, Valerio Manno, Carolina Mensi, Alessandro Marinaccio, Annibale Biggeri, Dolores Catelan.
       BACKGROUND: Italy, among the leading asbestos producers and users until the national ban in 1992, continues to register a high burden of asbestos-related diseases, mainly due to their long latency and delays in remediation. This study investigates the spatio-temporal evolution of pleural mesothelioma (PM) mortality over the past 40 years.
    MATERIALS AND METHODS: Malignant pleural tumours and PM deaths (1980-2020) were extracted from the national death registry, adjusted for misclassification of pleural tumours, and analysed by region and birth cohort (1905-1984). The analyses by calendar period and cohort, stratified by sex assigned at birth, were followed by a space-cohort Bayesian Hierarchical Model with structured random effects for time (cohorts up to 1960-1969) and space (administrative regions).
    RESULTS: In Italy, from 1980 to 2020, 35 134 people died from PM (24 380 males and 10 754 females). A mortality decrease was observed in males after 2010-14 and in females after 2000-4. Mortality steadily declined in both males and females across cohorts after 1935-44. The space-time analysis enabled the clear identification of the Italian regions most affected by PM.
    CONCLUSION: Italy's trend mirrors those of other Western countries that have banned asbestos, with the highest risks for birth cohorts in working age before the ban. The results reveal distinct spatio-temporal patterns, with the northern regions exhibiting the highest rates. The Italian experience with asbestos-related diseases detection could help other countries to assess the impact of asbestos, raise awareness, and promote a global ban on asbestos.
    Keywords:  asbestos; birth cohort; epidemiologic surveillance; mesothelioma; mortality; space-cohort Bayesian model
    DOI:  https://doi.org/10.1093/ije/dyaf227
  6. Adv Ther. 2026 Jan 28.
    Treatment Patterns, Clinical Outcomes, Health Care Resource Use, and Costs in Older Adults with Malignant Pleural Mesothelioma in the United States, 2007-2020.
    Himani Aggarwal, Ashwini Arunachalam, Jae Min, Yu-Han Kao, Haidong Feng, Danmeng Huang, Gloria Odonkor.
       INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare malignancy typically attributed to occupational asbestos exposure and associated with dismal survival outcomes. The standard of care for unresectable MPM was platinum-based chemotherapy until the approval of immunotherapy in 2020. We examined treatment patterns, clinical outcomes, health care resource use (HCRU), and costs in patients with MPM to understand disease burden before the first immunotherapy approval.
    METHODS: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare deidentified database in the US to select patients aged ≥ 65 years who initiated first-line therapy (1L, index event) for advanced MPM (regional extension or distant) diagnosed between 2007 and 2019. Eligible patients had continuous Medicare enrollment from the diagnosis date to ≥ 3 months post-index date, with ≥ 6-month follow-up after 1L initiation. Kaplan-Meier methods were used to estimate real-world time to treatment discontinuation (rwTTD) and overall survival (OS). Data cutoff was December 31, 2020.
    RESULTS: Among 554 patients with MPM who initiated 1L, median age was 74 years; most were white (95.0%) and male (73.7%). The most common 1L regimens were platinum-pemetrexed (75.6%), pemetrexed monotherapy (8.5%), and bevacizumab-platinum-pemetrexed therapy (8.1%); the median rwTTD of 1L therapy was 5.3 (95% CI, 4.2-6.3) months. Of 554 patients, 300 (54.2%) initiated second-line therapy (2L), and 120 (21.7%) initiated third-line therapy (3L). Platinum-pemetrexed (25.0%) and gemcitabine (25.0%) were the most common 2L and 3L, respectively. Median OS was 16.3 (95% CI, 15.4-17.8) months, with 5-year survival of 7.9% (95% CI, 5.5-10.9). Mean per-patient-per-month all-cause inpatient admissions, outpatient visits, emergency department visits, and total costs were 0.04, 1.74, 0.18, and $11,432, respectively.
    CONCLUSION: The study highlights a substantial clinical and economic burden among patients with advanced MPM who received 1L chemotherapy in the years preceding immunotherapy approvals, underscoring the need for more effective therapies to improve outcomes.
    Keywords:  Health care resource use; Malignant pleural mesothelioma; Overall survival; Real-world time to treatment discontinuation; Treatment patterns
    DOI:  https://doi.org/10.1007/s12325-025-03478-z
  7. Clin Lung Cancer. 2026 Jan 01. pii: S1525-7304(25)00338-9. [Epub ahead of print]27(2): 75-79
    Pembrolizumab Plus Platinum Doublet Chemotherapy With Lenvatinib in Unresectable Pleural Mesothelioma as First-Line Treatment (PENINSULA): A Study Protocol for a Single-Arm, Multi-Institutional, Phase II Clinical Trial.
    Tetsuya Takagawa, Kanae Takahashi, Yuji Orimoto, Yukie Morisaki, Shinichiro Suna, Takashi Daimon, Takashi Kijima, Kozo Kuribayashi.
       BACKGROUND: In pleural mesothelioma (PM), platinum-based chemotherapy and immune checkpoint inhibitors including nivolumab and ipilimumab have been approved but have not shown sufficient therapeutic efficacy, and the development of new therapies is desired. Pembrolizumab, anti-PD-1 antibody and lenvatinib which has inhibitory effect of angiogenesis are also expected to have a therapeutic effect on PM.
    PATIENTS AND METHODS: Twenty-five patients will be enrolled in PENINSULA trial. In induction treatment, study interventions include oral lenvatinib, 8 mg QD, and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion. In maintenance treatment, participants may receive lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and pembrolizumab may be given for up to a total of 35 courses. The primary endpoint is overall response rate. The secondary endpoints are progression-free survival, overall survival time, tumor shrinkage (disease control rate), duration of response, best overall response and safety evaluation.
    CONCLUSION: The purpose of this clinical trial is to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab and standard chemotherapy as first-line therapy in adult patients with PM.
    Keywords:  Combination therapy; Immune checkpoint inhibitor; Multicenter study; Multikinase inhibitors; Phase II trial
    DOI:  https://doi.org/10.1016/j.cllc.2025.12.010
  8. Cancers (Basel). 2026 Jan 09. pii: 221. [Epub ahead of print]18(2):
    The Diagnostic Trap in Radiation-Induced Mesothelioma: Kinetic-Morphological Decoupling Masks Molecular Aggression.
    Norikatsu Fujita, Katsumi Fujita, Hironobu Osumi, Yoshiyasu Takefuji.
      Background: In malignant pleural mesothelioma, epithelioid histology is traditionally considered a favorable prognostic marker. However, it remains clinically undetermined whether the intensity of an oncogenic insult can disrupt this link. Radiation-induced cases serve as an unconfounded biological model to dissect such trajectories masked by asbestos confounding. Methods: We performed an Individual Patient Data (IPD) synthesis of 20 strictly asbestos-unexposed human cases, applying clinically established dose stratification (intermediate: 20-45 Gy vs. high: >45 Gy). To confirm the observed pattern, we examined data from 829 dogs in the Colorado State University (CSU) Beagle Study. Results: In the intermediate-dose group (n = 13), a significant positive correlation persisted between age at radiotherapy and the latent period (ρ = 0.567, p = 0.043). Conversely, high-dose exposure (>45 Gy) showed a disruption of this age-dependent pattern, with a trend toward inverse correlation (ρ = -0.754, p = 0.084). Interaction analysis confirmed a statistically significant divergence between these dose-dependent trends (p = 0.005). The CSU Beagle Study (n = 829) demonstrated the physical basis of this phenomenon: in the canine model, high-dose exposure (≥0.74 Gy) triggered a "Step-Jump" in cumulative incidence (30.4% at 0.5 years), indicating instantaneous carcinogenic onset distinct from cumulative biological aging. Conclusions: This kinetic divergence points to a "Diagnostic Trap." We propose a 'Single- to Double-Brake' framework where intermediate doses preserve age-dependent progression, whereas high doses likely trigger catastrophic genomic failure (chromothripsis) that bypasses the time required for morphological dedifferentiation. Consequently, morphologically indolent epithelioid tumors in high-dose survivors may harbor aggressive molecular profiles not predicted by histology alone, necessitating risk-stratified precision surveillance.
    Keywords:  CDK4/6 inhibitors; CDKN2A; CSU Beagle Study; chromothripsis; diagnostic trap; kinetic-morphological decoupling; malignant pleural mesothelioma; precision medicine; radiation-induced cancer; therapeutic stratification; tumor suppressor genes
    DOI:  https://doi.org/10.3390/cancers18020221
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