bims-mesote 2026-05-10 papers

Issue of 2026–05–10
four papers selected by
Laura Mannarino, Humanitas Research

Clin Nucl Med. 2026 Apr 16.

Dramatic Morphometabolic Response to Bevacizumab-Based Chemotherapy After Immunotherapy Failure in Malignant Pleural Mesothelioma on FDG PET.

Kevser Oksuzoglu, Lutfu Perktas, Hasan Onner, Farise Yilmaz.

Malignant mesothelioma is a rare but highly aggressive malignancy associated with a poor prognosis. Similar to many other solid tumors, cytotoxic chemotherapy has traditionally been the standard treatment for patients with locally advanced or metastatic malignant pleural mesothelioma (MPM). However, with increasing recognition of immune dysregulation, immune-directed therapies have assumed a growing role in the management of mesothelioma. Here, we report a case of epithelioid-type malignant pleural mesothelioma that demonstrated primary resistance to ipilimumab plus nivolumab, followed by a marked metabolic response on 18F-FDG PET/CT after switching to bevacizumab plus pemetrexed plus carboplatin.

Keywords: 18F-FDG PET/CT; immunotherapy; mesothelioma

DOI: https://doi.org/10.1097/RLU.0000000000006495

JTCVS Open. 2026 Apr;30 101603

Real-world outcomes of multimodal treatment for pleural mesothelioma: A retrospective study in a high-volume integrated regional center.

Alison S Baskin, Keza Levine, Yun-Yi Hung, Elaine Liang, Kian C Banks, J Marie Suga, Jeffrey B Velotta.

Objective: To evaluate overall survival (OS) associated with multimodal treatment regimens, including pleurectomy/decortication (PD) and systemic therapy, in patients with clinical stage I-II epithelioid pleural mesothelioma (PM).
Methods: We identified patients with PM treated within an integrated health care system (2009-2023). We grouped patients by treatment: no treatment, surgery, systemic therapy, and multimodal treatment (surgery + systemic therapy). The primary outcome was median OS. Using multivariable Cox regression, we assessed associations between treatment and OS, adjusting for clinical characteristics. Subgroup analyses were performed for patients with clinical stage I-II epithelioid PM.
Results: Among all eligible patients (n = 432), those who received no treatment (n = 198), surgery (n = 25), systemic therapy (n = 164), and multimodal treatment (n = 45) had median OS of 5 months (95% CI, 4-7), 11 (6-17), 13 (12-17), and 27 (20 to nonestimable [NE]) (P < .0001). Among patients with clinical stage I-II epithelioid PM (n = 112), those who received no treatment (n = 40), surgery (n = 10), systemic therapy (n = 42), and multimodal treatment (n = 20) had median OS of 10 (7-17), 29 (5-NE), 18 (17-26), and 37 (25-NE) months (P < .0005). Adjusted analyses showed improved OS relative to no treatment with multimodal treatment but not systemic therapy in the clinical stage I-II epithelioid subgroup (multimodal therapy: adjusted hazard ratio, 0.35; 95% CI, 0.15-0.85, P = .02; systemic therapy: adjusted hazard ratio, 0.66; 95% CI, 0.37-1.16, P = .15).
Conclusions: In a real-word cohort of patients with early-stage epithelioid PM, multimodal treatment incorporating surgery and systemic therapy was associated with improved OS compared with no treatment. These findings reinforce the benefit of surgery in carefully selected patients, despite recent studies questioning its role in a broader population.

Keywords: decortication; early-stage; epithelioid; multimodal therapy; pleural mesothelioma (PM); pleurectomy

DOI: https://doi.org/10.1016/j.xjon.2026.101603

Diagnostics (Basel). 2026 Apr 11. pii: 1142. [Epub ahead of print]16(8):

MiR-21 Is a Novel Diagnostic and Prognostic Circulating Biomarker in Pleural Mesothelioma.

Berta Mosleh, Yawen Dong, Elisabeth Lang, Thomas Klikovits, Katharina Sinn, Steven Kao, Marko Jakopovic, Clemens Aigner, Balazs Hegedüs, Natalie Baldes, Servet Bölükbas, Balazs Dome, Mir Alireza Hoda, Viktoria Laszlo, Michael Grusch, Karin Schelch.

Background/Objective: The identification of novel non-invasive diagnostic and prognostic biomarkers is urgently needed in pleural mesothelioma (PM). While soluble mesothelin-related peptides (SMRP) are the most established circulating biomarker, their prognostic value is limited. A wide range of microRNAs (miRs) play diverse roles in regulating gene expression in PM. MiR-21 has been shown to be upregulated in mesothelioma tissue; nevertheless, the diagnostic and prognostic utility of miR-21 in the circulation and its association with survival in PM have not been extensively investigated to date. The objective of the current study was to evaluate miR-21 as a potential blood-based diagnostic and prognostic biomarker in PM. Methods: Plasma samples from PM patients (n = 94) were collected at the time of diagnosis, prior to treatment. Sex- and age-matched healthy individuals (n = 30) served as controls. MiR-21 levels were measured using quantitative RT-PCR and normalized to miR-16, and potential correlations with clinicopathological data were analyzed. Serum SMRP levels were measured in matched patients (n = 84), and a direct comparative analysis of miR-21 and SMRP was conducted. In situ hybridization (ISH) was used to confirm the presence of miR-21 in tumor cells. Results: Plasma miR-21 levels were significantly elevated in PM patients compared to healthy controls (p < 0.001), demonstrating good diagnostic performance (AUC 0.81). The localization of miR-21 in PM cells was confirmed by ISH. High miR-21 levels were associated with significantly shorter median overall survival (12.4 vs. 24.3 months, p < 0.001). Elevated SMRP levels were also associated with reduced survival (12.4 vs. 19.5 months, p = 0.032); however, SMRP did not retain independent prognostic significance in multivariable analysis. In contrast, high-circulating miR-21 was confirmed as an independent predictor for poor survival (HR 3.12, p < 0.001). Conclusions: Our findings highlight that circulating miR-21 is a potential non-invasive biomarker with both diagnostic and independent prognostic value in pleural mesothelioma and outperforms SMRP in multivariable survival analysis. Further research is warranted to validate its role in the biology of this disease and to assess its correlation with outcome and treatment responses.

Keywords: SMRP; circulating biomarker; microRNA-21; pleural mesothelioma

DOI: https://doi.org/10.3390/diagnostics16081142

Cell Death Dis. 2026 May 02.

BAP1 and USP1 cooperate to regulate FANCD2 stability and cell proliferation in mesothelioma cells.

Koya Suzuki, Shinichi Kiyonari, Jo Nishino, Miki Takahashi, Yuna Kato, Miki Amano, Anna Ogiso, Tomohiro Akashi, Tohru Maeda, Norio Kaneda, Takashi Miida, Yutaka Kondo, Kenji Kadomatsu, Mamoru Kato, Koji Aoyama, Hiroshi Murakami, Yoshitaka Sekido, Yuko Murakami-Tonami.

BRCA1-associated protein 1 (BAP1) is frequently inactivated in pleural mesothelioma and functions as a tumor suppressor through its deubiquitinating activity. In this study, we investigated the context-dependent interplay between BAP1 and ubiquitin-specific protease 1 (USP1) in mesothelioma cells, focusing on their roles in regulating FANCD2, cell proliferation, and DNA damage responses. Genetic suppression of USP1 selectively inhibited cell proliferation in BAP1-deficient mesothelioma cells, whereas reintroduction of wild-type BAP1 rescued this growth defect; notably, a catalytically inactive BAP1 mutant failed to do so, indicating that BAP1 deubiquitinase activity is required for this compensation. In contrast, depletion of FANCD2 suppressed cell proliferation irrespective of BAP1 status, underscoring the essential role of FANCD2 in mesothelioma cell survival. Although both BAP1 and USP1 were capable of deubiquitinating FANCD2 in vitro, USP1 suppression in mesothelioma cells did not provide clear biochemical evidence of altered FANCD2 ubiquitination. Instead, USP1 knockdown was associated with reduced FANCD2 transcript and protein levels, without markedly affecting FANCD2 mRNA stability. At the cellular level, USP1 depletion impaired FANCD2 focus formation and reduced its colocalization with γ-H2AX in BAP1-deficient cells, consistent with defective DNA damage signaling. Despite these changes, homologous recombination (HR) efficiency was largely preserved, whereas non-homologous end joining activity was modestly increased upon USP1 suppression. Consistent with these in vitro findings, USP1 knockdown suppressed tumor growth in an intrathoracic xenograft model. Collectively, our results indicate that BAP1 and USP1 appear to regulate FANCD2 through distinct, context-dependent mechanisms, with USP1 primarily influencing FANCD2 expression and BAP1 modulating FANCD2 function at the post-translational level. Together, these findings identify USP1 as a context-dependent therapeutic vulnerability in BAP1-deficient mesothelioma and support a working model in which USP1-dependent maintenance of FANCD2 function becomes critical in the absence of functional BAP1.

DOI: https://doi.org/10.1038/s41419-026-08818-7