bims-mesote 2026-04-26 papers

Issue of 2026–04–26
seven papers selected by
Laura Mannarino, Humanitas Research

BMC Pulm Med. 2026 Apr 24.

Diagnosis and management of pleural mesothelioma: three unique cases and review of the literature.

Zeina Al Achkar, Dany Gaspard, Mirella Iskandar.

Keywords: Asbestos exposure; Biphasic mesothelioma; Epithelioid mesothelioma; Extrapleural pneumonectomy; Immunohistochemistry; Mesothelioma; Pleural mesothelioma; Sarcomatoid mesothelioma; Synchronous malignancy

DOI: https://doi.org/10.1186/s12890-026-04316-w

Thorac Cancer. 2026 Apr;17(8): e70259

Emerging Strategies in the Diagnosis and Treatment of Pleural Mesothelioma: An Overview.

Raffaella Pagliaro, Beatrice Leonardi, Angela Schiattarella, Grazia Bergameo, Carmine Picone, Adolfo Gallipoli D'Errico, Filippo Scialò, Fabio Perrotta, Maria Luisa De Rimini, Alfonso Fiorelli, Andrea Bianco.

Pleural mesothelioma (PM) is a rare and aggressive cancer arising from pleural mesothelial cells with a strong association to asbestos exposure. Among the diagnostic strategies available are noninvasive techniques including thoracic ultrasound (TUS), computed tomography (CT) scans, positron emission tomography (PET-CT), and invasive procedures such as thoracoscopy and pleural biopsy. Accurate identification of the histological subtype is critical for tailoring treatment strategies. The standard treatment for unresectable PM has traditionally been chemotherapy, particularly platinum and pemetrexed. However, recent advances in translational clinical research, including immune checkpoint inhibitors (ICIs), are changing the therapeutic landscape, offering new opportunities for personalized treatment. The recent FDA approval of nivolumab and ipilimumab combination therapy as a first-line treatment has significantly improved outcomes, especially for nonepithelioid subtypes. Ongoing studies are exploring additional immune-targeted therapies such as VISTA, LAG-3, and dendritic cell-based therapies. Early detection, refined biomarker identification, and a deeper understanding of the tumor microenvironment remain essential to improving PM prognosis and patient survival. This review provides a comprehensive exploration of the epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and molecular markers), staging, and current treatment strategies for PM.

Keywords: asbestos; biomarkers; chemotherapy; clinical diagnosis; immunotherapy; pleural mesothelioma (PM); radiotherapy; surgery

DOI: https://doi.org/10.1111/1759-7714.70259

J Am Soc Cytopathol. 2026 Mar 28. pii: S2213-2945(26)00041-4. [Epub ahead of print]

Checkpoint kinase 1 protein as a diagnostic marker for pleural mesothelioma.

Azadeh Asghari Birbaneh, Christos Meristoudis, Caspar Bundgaard Nielsen, Weronika Maria Szejniuk, Morten Johansen, Peter Derek Christian Leutscher, Vasiliki Panou, Oluf Dimitri Røe.

INTRODUCTION: Pleural mesothelioma (PM) is an aggressive malignancy that poses diagnostic challenges, particularly in cytological specimens. Checkpoint kinase 1 (CHK1); a pivotal mediator of genomic stability, has been identified as a promising therapeutic target. In this study, we investigate CHK1 protein expression in PM and evaluate its potential utility as a diagnostic biomarker.
MATERIALS AND METHODS: This retrospective study included patients diagnosed with PM and control cases containing non-neoplastic mesothelial cells (NNMC). Tissue microarrays were immunostained for CHK1 protein. Diagnostic accuracy of CHK1 expression was assessed across tumor subtypes (epithelioid and nonepithelioid) and specimen types (cytology and histology), using dichotomized positivity. CHK1 expression levels were compared between tumor subtypes and specimen types using the histoscore method.
RESULTS: A total of 152 pm cases were included (cytology, n = 74; histology, n = 78), along with 33 cytological control cases. CHK1 expression significantly distinguishes PM from NNMC (P < 0.001), with ranging sensitivities (67%-100%) and specificities (75%-91%), depending on subcellular localization and tumor subtypes. Nuclear expression contributes to high sensitivity whereas cytoplasmic expression confers the highest specificity. The histoscores were higher for total and nucleus in histology compared to cytology, while no significant differences in expression were observed between epithelioid and nonepithelioid PM.
CONCLUSIONS: Immunohistochemical assessment of CHK1 expression may be useful for distinguishing PM from NNMC. Robust diagnostic sensitivity was observed across both epithelioid and nonepithelioid PM, independent of specimen type. These support CHK1 as a potential pan-mesothelioma diagnostic biomarker. Further validation is warranted in larger, independent cohorts.

Keywords: Checkpoint kinase 1 protein; Diagnostic biomarkers; Effusion cytology; Immunohistochemistry; Mesothelial cells; Pleural mesothelioma

DOI: https://doi.org/10.1016/j.jasc.2026.03.004

Ann Thorac Surg. 2026 Apr 20. pii: S0003-4975(26)00345-0. [Epub ahead of print]

The Society of Thoracic Surgeons 2026 Expert Consensus on the Multimodal Treatment of Pleural Mesothelioma.

Jeffrey B Velotta, Anja C Roden, Jonathan Rice, Charles B Simone, Bansari Upadhyay, Pallavi Sood, Daniel L Miller, R Taylor Ripley, Andrea Wolf, Bryan M Burt, Samuel S Kim, Isabelle Opitz, Hedy L Kindler, Harvey I Pass, J W Awori Hayanga, Valerie Rusch, Raphael Bueno.

BACKGROUND: Pleural mesothelioma (PM) is a rare and complex thoracic malignancy for which treatment regimens continue to evolve. The role of surgery in the management of PM is controversial. We reviewed contemporary literature to provide consensus recommendations from an expert multidisciplinary panel on the multimodal treatment of PM with an emphasis on surgical intervention in order to update management pathways.
METHODS: An international, multidisciplinary panel developed PICO-based (Population, Intervention, Comparator, Outcomes) questions and conducted a comprehensive literature review to identify relevant literature. Consensus statements were developed using a modified Delphi process with at least 75% agreement over three voting rounds.
RESULTS: A total of 13 PICO questions were developed, and detailed summary statements were provided for each PICO subtopic based on systematic literature review and multidisciplinary expert panel discussion. There was strong consensus that accurate diagnosis depends on adequate pleural biopsy specimens and that clinical evaluation should include at a minimum CT and PET imaging. Therapeutic decisions should be discussed by a multidisciplinary tumor board including thoracic surgeons with expertise in PM treatment. If surgical resection is deemed appropriate, it should be part of a multimodal treatment plan. Pleurectomy/Decortication (P/D) or Extended Pleurectomy/Decortication (EPD) is strongly favored over Extrapleural Pneumonectomy (EPP) as the approach to resection.
CONCLUSIONS: This STS Expert Consensus Document includes contemporary treatment recommendations for PM based on systematic literature review and multidisciplinary expert panel discussion and provides a management framework for practicing thoracic surgeons.

DOI: https://doi.org/10.1016/j.athoracsur.2026.03.074

NPJ Precis Oncol. 2026 Apr 18.

Therapeutic vulnerabilities exposed by the 9p21 loss identified through multiparametric drug screening inform rational combination strategies.

Riccardo Bevilacqua, Paola Gasperini, Thomas Cantore, Catarina Macedo-Silva, Michael Pancher, Martina Radić, Haiyan Yue, Orsetta Quaini, Tarcisio Fedrizzi, Pamela Gatto, Roland Seiler, Bernhard Kiss, Valentina Adami, Francesca Lorenzin, Marianna Kruithof-de Julio, Bishoy Morris Faltas, Francesca Demichelis.

Homozygous loss of the 9p21 locus encompassing CDKN2A, CDKN2B, and MTAP is the most frequent copy number alteration across tumor types, making it a promising target for precision medicine strategies. To explore drug vulnerabilities exposed by this loss, we generated 9p21 locus isogenic bladder cancer (BLCA) cell models to perform a multiparametric drug screen, testing 2,349 compounds. We identified cytarabine and methotrexate as significantly more effective in the 9p21 compromised BLCA cells. Analysis of morphological alterations further supported a genotype-specific activity of nucleoside analogs, nominating gemcitabine as a drug with greater efficacy in this context. To further exploit MTAP loss, we explored drug combinations targeting MTAP synthetic lethal partners, PRMT5 and MAT2A. Synergy between cytarabine and inhibitors of PRMT5 (MRTX1719) and MAT2A (AG-270) was mediated by a differential activation of DNA damage and replication stress markers, suggesting an exploitable vulnerability. In fact, rational drug combinations with ATR/CHK1 pathway inhibitors increased efficacy while maintaining 9p21-specificity. Finally, we confirmed the effectiveness of these combinations in cell models of pancreatic adenocarcinoma and pleural mesothelioma, two tumor types with high prevalence of MTAP loss and, most notably, in bladder cancer patient-derived organoids, underscoring the strong translational potential of our findings.

DOI: https://doi.org/10.1038/s41698-026-01434-w