bims-mesote 2026-03-29 papers

Issue of 2026–03–29
six papers selected by
Laura Mannarino, Humanitas Research

BMC Cancer. 2026 Mar 26.

Gemcitabine as maintenance treatment of diffuse pleural mesothelioma: randomized phase II study.

Mohamed Emam Sobeih, Maha Helal, Maha Yahia, Ola Khorshid.

Keywords: Best Supportive Care; Gemcitabine; Maintenance Therapy; Malignant Pleural Mesothelioma; Platinum-Based Chemotherapy

DOI: https://doi.org/10.1186/s12885-026-15836-3

J Thorac Cardiovasc Surg. 2026 Mar 23. pii: S0022-5223(26)00792-0. [Epub ahead of print]

A Phase 1/1b Study of Direct Intratumoral Injection of Pleural Mesothelioma of Immunostimulant Prior to Surgical Resection.

Andrea S Wolf, Shubham Gulati, Komal Dolasia, Bailey Fitzgerald, Jorge Gomez, David Yankelevitz, Andres Salazar, Alexander M Tsankov, Thomas Marron, Raja Flores.

OBJECTIVE: This window of opportunity phase 1/1b clinical trial evaluated the role of neoadjuvant injection of the viral mimic poly-ICLC in patients with pleural mesothelioma undergoing curative-intent surgical resection.
METHODS: Patients with documented pleural mesothelioma who were deemed resectable underwent intratumoral injection of poly-ICLC 2-4 weeks prior to planned curative-intent surgery. Safety and toxicity were the primary endpoints and secondary endpoints were postoperative complications, mortality, and overall survival, with patients censored at the date of last follow-up if not known to be deceased.
RESULTS: From 2020 to 2024, 19 patients underwent treatment followed by pleurectomy/decortication a median of 19 days (range 14-192) later. Poly-ICLC was well tolerated with drug-related Grade I toxicities occurring in 7 (37%) patients. All patients were resectable and the diaphragm and pericardium preserved. Median length of stay was 7 days (range 3-19), post-operative complications were minor, except one cardiac arrest due to complete heart block and there were no deaths within 90 days of surgery. Median overall survival was 19.6 months from injection (95% CI: 14.7-NR) and 19.1 (95% CI: 13.4-NR) from surgery. One patient whose surgery was delayed and underwent systemic chemotherapy following injection was found to have complete response to poly-ICLC and systemic treatment.
CONCLUSIONS: This prospective clinical trial is the first to demonstrate the safety of intratumoral injection of poly-ICLC with excellent surgical results and favorable survival, with one patient experiencing dramatic response to injection and chemotherapy. Use of poly-ICLC as an immunostimulant with combinatorial strategies offers hope for treating this challenging disease.

Keywords: Cancer Vaccine; Mesothelioma; Neoadjuvant Therapy; Pleurectomy/Decortication

DOI: https://doi.org/10.1016/j.jtcvs.2026.03.594

Pharmaceuticals (Basel). 2026 Mar 18. pii: 501. [Epub ahead of print]19(3):

Radioimmunotherapy for Malignant Mesothelioma Targeting C-ERC/Mesothelin.

Hirofumi Hanaoka, Aiko Yamaguchi, Masahiro Maeda, Tatsuya Segawa, Noboru Oriuchi.

Background/Objectives: Malignant mesothelioma has a poor prognosis and limited therapeutic options. C-ERC/mesothelin is highly expressed in mesotheliomas and is a potential target for radioimmunotherapy (RIT). This study evaluated the radiolabeled anti-C-ERC/mesothelin antibody mAb 22A31 as a therapeutic agent. Methods: C-ERC/mesothelin expression in mesothelioma cell lines was assessed by Western blotting, and the specific binding of 125I-labeled mAb 22A31 was examined. Biodistribution of 111In-labeled mAb 22A31 was evaluated in a mesothelioma cell line, MSTO-211H tumor-bearing mice. The therapeutic efficacy of 90Y-labeled mAb 22A31 was evaluated in subcutaneous and pleural dissemination models. Results: mAb 22A31 showed specific binding considering the level of C-ERC/mesothelin expression in each mesothelioma cell line. 111In-mAb 22A31 accumulated in tumors with minimal uptake in normal tissues. 90Y-mAb 22A31 significantly delayed the growth of subcutaneous tumors and improved survival in a pleural dissemination model. Conclusions: Radiolabeled mAb 22A31 specifically targeted C-ERC/mesothelin and demonstrated therapeutic efficacy in a mesothelioma xerograph model. Therefore, 90Y-mAb 22A31 is a promising RIT agent and supports the further development of C-ERC/mesothelin-targeted therapy for mesothelioma.

Keywords: C-ERC/mesothelin; malignant mesothelioma; radioimmunotherapy

DOI: https://doi.org/10.3390/ph19030501

Front Oncol. 2026 ;16 1739494

Case Report: Immune checkpoint inhibitor-triggered anti-Ma2 paraneoplastic encephalitis in sarcomatoid pleural mesothelioma: a fatal case.

Ilker Nihat Okten, Tuba Baydaş.

Background: Neurological immune-related adverse events (N-irAEs) represent rare but potentially fatal complications of immune checkpoint inhibitor (ICI) therapy. Among these, encephalitis associated with paraneoplatic neuronal antibodies poses a major diagnostic and therapeutic challenge, as it blurs the distinction between drug-induced toxicity and tumor-driven autoimmunity.
Case presentation: We report a 61-year-old male diagnosed with unresectable sarcomatoid pleural mesothelioma who was treated with first-line nivolumab plus ipilimumab. Following the third treatment cycle, the patient developed progressive hyperphagia, central sleep apnea, and autonomic dysfunction. Serum testing revealed strong positivity for anti-Ma2/Ta antibodies, while brain magnetic resonance imaging was unremarkable. Despite discontinuation of immunotherapy and treatment with high-dose corticosteroids and intravenous immunoglobulin, the patient experienced relentless neurological deterioration. Notably, follow-up positron emission tomography demonstrated complete metabolic tumor response. The patient ultimately died from progressive brainstem dysfunction.
Discussion: Anti-Ma2-associated encephalitis is classically categorized as a paraneoplastic neurological syndrome mediated by cytotoxic T-cell responses against intracellular neuronal antigens. Recent evidence suggests that ICIs can unmask or accelerate latent paraneoplastic autoimmunity by amplifying pre-existing immune responses. In this context, our case is best interpreted as an ICI-triggered paraneoplastic neurological syndrome rather than a primary immune-related adverse event.
Conclusion: This case highlights a fatal neurological complication occurring in parallel with complete oncologic remission, underscoring the paradox of effective cancer immunotherapy precipitating catastrophic immune-mediated neurotoxicity. Early recognition of prodromal neurological symptoms and heightened awareness of paraneoplastic syndromes in the ICI era are critical to improving patient outcomes.

Keywords: anti-Ma2 encephalitis; immune checkpoint inhibitors; neuroimmunology; paraneoplastic neurological syndrome; pleural mesothelioma

DOI: https://doi.org/10.3389/fonc.2026.1739494

Mol Metab. 2026 Mar 23. pii: S2212-8778(26)00040-2. [Epub ahead of print] 102356

Dynamic Evaluation Of The Glycolytic Determinants LDH-A And GLUT-1 Enhances Prognostic Significance And Their Inhibition Affect The Growth Of Mesothelioma Spheroids.

Marika A Franczak, Federica Borea, Valentina Donati, Marta Aliprandi, Amir Avan, Valentina Doldi, Giulia Bononi, Kin Yip Tam, Carlotta Granchi, Ryszard T Smolenski, Paolo A Zucali, Filippo Minutolo, Godefridus J Peters, Elisa Giovannetti.

Energy metabolism plays a crucial role in determining the aggressiveness of cancer. In this study, we assessed the impact of drug-induced modulation on the expression and prognostic significance of crucial factors involved in glycolytic metabolism: lactate dehydrogenase A (LDH-A) and glucose transporter type 1 (GLUT-1). In patient samples diagnosed with pleural Malignant Mesothelioma (MM), expression levels of LDH-A and GLUT-1 were studied both at baseline and after platinum-based-chemotherapy. High GLUT-1 and LDH-A levels were associated with shorter survival, and chemotherapy increased GLUT-1 expression, further correlating with poor prognosis. Utilizing LDH-A (NHI-2) and GLUT-1 (PGL14) inhibitors, we examined their effects on migration and apoptosis in immortalized (H2052, H2452) and primary (STO, MESO-II) MM cells. PGL14 and NHI-2 decreased migration, increased reactive oxygen species (ROS) and apoptosis rates. Inhibitors, both single and in combination, disintegrated the MM spheroids, while the bioluminescence from spheroid-forming cells decreased from 1.3x105 in the control group to 9.7x104 and 7.1x104 [RLU/s] after NHI-2 and PGL14/NHI-2 treatment, respectively. Overexpression and chemotherapy-induced modulation of LDH-A and GLUT-1 correlated with poor MM prognosis. Combined inhibition of these two metabolic determinants impeded MM cell migration, stimulated ROS production and apoptosis, and affected spheroids' growth, offering promise for new treatment development.

Keywords: chemoresistance; glucose transporter-1; lactate dehydrogenase-A; malignant mesothelioma; new inhibitors of glycolytic metabolism

DOI: https://doi.org/10.1016/j.molmet.2026.102356

Life (Basel). 2026 Feb 28. pii: 385. [Epub ahead of print]16(3):

Inactivation of BAP1 and the Hippo Pathway Characterizes the Genomic Alterations of Peritoneal Mesothelioma.

Maya Samuels, Madi Williams, Angela Hasan, Susan Rafie, Grace S Saglimbeni, Beau Hsia, Sunil Nair, Sweety Aeilias, Abubakar Tauseef.

BACKGROUND/OBJECTIVES: Peritoneal mesothelioma is a rare malignancy characterized by limited therapeutic options and a poor prognosis. Genomic characterization can enhance the understanding of the molecular mechanisms that lead to this disease and can contribute to improved survival outcomes through therapeutic targets.
METHODS: Analysis was performed using a dataset from the AACR GENIE database (v17.0-public) comprising 204 samples from 192 patients. Data were analyzed to identify patterns in genomic alterations and clinical demographics. Within the GENIE cohort, histologic subtype information was incomplete and inconsistently reported across contributing institutions. Hence, histological subtype genomic analysis was not viable.
RESULTS: The most common somatic mutation was found in the BAP1 gene (25.98%). Other common mutations were found in the NF2 (15.19%), TP53 (9.3%) and SETD2 (8.3%) genes. Several pathways were found as potential treatment targets including the chromatin remodeling, Hippo, and p53 signaling pathways. Given the size of our dataset, we were unable to draw significant conclusions about certain demographics.
CONCLUSIONS: This study presents data that can help draw conclusions on common mutations, mutual exclusivity patterns, and demographics at risk for peritoneal mesothelioma. Genomic analysis of peritoneal mesothelioma may inform possible intervention targets for therapeutic treatment.

Keywords: AACR Project GENIE; BAP1; NF2; TP53; hippo signaling pathway; p53; peritoneal mesothelioma; somatic mutations; tumor suppressor genes

DOI: https://doi.org/10.3390/life16030385