bims-mesote 2025-10-05 papers

Issue of 2025–10–05
five papers selected by
Laura Mannarino, Humanitas Research

Lung Cancer. 2025 Sep 28. pii: S0169-5002(25)00661-0. [Epub ahead of print]209 108769

Discovery of actionable drug targets to enhance T-cell infiltration and immune checkpoint blockade efficacy in pleural mesothelioma.

Jasper H L T van Genugten, Daniel Faulkner, Jens C Hahne, Charlotte Poile, Lodewyk Wessels, Dean A Fennell, Paul Baas.

BACKGROUND: Malignant pleural mesothelioma (PM) is an aggressive cancer with limited treatment options. Although first-line nivolumab plus ipilimumab improves outcomes for some patients, a majority fail to respond. Mechanisms of immune resistance in PM remain poorly understood, underscoring the need for new clinically actionable drug targets to overcome immunotherapy resistance.
METHODS: We established an in silico pipeline to investigate the molecular basis of T-cell exclusion in bulk RNA-sequencing data from 448 patients across three immune checkpoint blockade (ICB)-naïve PM cohorts. We assessed genome-wide correlations between gene expression and a previously validated cytotoxic T-cell signature score. Candidate immune evasion genes were prioritized based on clinical relevance, drug availability, and experimental feasibility for follow-up translational research.
RESULTS: The in silico pipeline produced a highly reproducible catalogue of genes whose expression inversely correlates with T-cell infiltration, including established immune evasion factors (e.g. SOX4, KDM5B, CMTM4) and five novel FDA-approved drug targets (SMO, GANAB, ERBB2, GABRA1, ODC1). Seven additional targets (ARNT, BMPR1B, GSK3B, ACVR1, BACE1, RPS6KB1, ULK1) with preclinical inhibitors were also identified. Notably, we identified a possible link between primary cilia, Hedgehog signaling and T-cell exclusion. We found that SMO expression correlated with poor clinical response to second-line nivolumab plus ipilimumab in PM, highlighting SMO as a promising therapeutic target and potential biomarker for treatment resistance.
CONCLUSIONS: This comprehensive transcriptomic characterization of T-cell exclusion in PM reveals that targeting cilium-based Hedgehog signaling, in addition to multiple other actionable drug targets, could enhance the efficacy of ICB treatment in PM.

Keywords: Drug repurposing; Hedgehog signaling; Immune checkpoint blockade; Immune evasion; Malignant pleural mesothelioma; SMO inhibitor; Transcriptomics

DOI: https://doi.org/10.1016/j.lungcan.2025.108769

Transl Oncol. 2025 Sep 29. pii: S1936-5233(25)00278-5. [Epub ahead of print]62 102547

The role of non-coding RNAs in pleural mesothelioma.

Giulia Tonnini, Giulia Di Mauro, Maria Letizia Tramarin, Anna Meneghetti, Ilaria Bononi, Chiara Mazziotta, John Charles Rotondo, Elisa Mazzoni, Maria Rosa Iaquinta, Elisabetta Trabetti, Cristina Bombieri, Monica De Mattei, Mauro Tognon, Fernanda Martini.

BACKGROUND: Pleural mesothelioma (PM) is a rare and highly aggressive tumor, primarily caused by asbestos exposure. Its long latency period and late-stage diagnosis severely limit therapeutic options.
AIM: Recent evidence suggests that non-coding RNAs (ncRNAs)-including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)-play key roles in PM biology. This review aims to synthesize current knowledge on ncRNA dysregulation in PM and explore their diagnostic, prognostic, and therapeutic potential.
SCOPE: We summarize studies addressing the expression and function of ncRNAs in tumors and in circulating biofluids of PM patients. Particular attention is given to how ncRNAs regulate proliferation, apoptosis, and migration, and how competing endogenous RNA (ceRNA) networks shape gene regulation in PM.
NOVELTY AND CONCLUSION: Unlike previous reviews, this work integrates findings across different classes of ncRNAs and their interactions, highlighting the emerging concept of ceRNA networks in PM. By bridging molecular mechanisms with potential clinical applications, we provide an updated and comprehensive framework that may inform future strategies for diagnosis, prognosis, and targeted therapy in PM.

Keywords: Epigenetic modifications; Non-coding RNAs; PM; circRNAs; lncRNAs; miRNAs

DOI: https://doi.org/10.1016/j.tranon.2025.102547

Front Chem. 2025 ;13 1659283

Manganese-doped nanotheranostic system for MRI-guided photothermal therapy of malignant pleural mesothelioma: in vivo study.

Lichang Lei, Hongjiao Zi, ShaoLei Kang, Hui Duan, Zhenghua Zhang, Chao Gao, Ruoyun Xu, Dan Han.

Introduction: Magnetic Resonance Imaging (MRI)-guided photothermal therapy (PTT) holds significant promise for the treatment of solid tumors, however, its diagnostic and therapeutic efficacy in malignant pleural mesothelioma (MPM) remains underexplored. To address the limitations of traditional gadolinium (Gd)-based MRI contrast agents, such as intolerance in patients with renal insufficiency and T1 signal attenuation at high field strengths, as well as oxidative stress damage caused by manganese ion leakage from manganese-based materials, this study aims to develop highly chelated and stable manganese polydopamine (Mn-PDA) multifunctional nanoprobes for MRI monitoring and PTT treatment of MPM.
Methods: Mn2+ and dopamine were chelated into Mn-PDA NP nanospheres in an ethanol-water system. The physicochemical properties were characterized using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), zeta potential, Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Photoelectron Spectroscopy (XPS), and Electron Paramagnetic Resonance (EPR). The photothermal performance under 808 nm laser irradiation was also evaluated. The MRI imaging performance (longitudinal/transverse relaxation rates, r1/r2) and manganese ion deposition quantification of Mn-PDA NPs were evaluated in vitro and in vivo at 3.0 T MR scanner. Additionally, the PTT efficacy of Mn-PDA NPs was evaluated in MSTO-211H cells and xenograft tumor models. Biocompatibility was assessed through H&E staining of major organs and blood biochemical analyses.
Results: Mn-PDA NPs exhibited a spherical morphology with uniform size (~200 nm), along with high photothermal conversion efficiency, favorable T1-weighted MRI contrast enhancement and low cytotoxicity. At 8 hours post-injection in vivo, Mn-PDA NPs resulted in a 42.9% enhancement in T1-weighted MRI signals within MPM tumors, accompanied by specific tumor accumulation. Under 808 nm laser irradiation, Mn-PDA NPs inhibited MPM tumor growth, as evidenced by reduced tumor volume, expanded areas of tumor necrosis (H&E staining), and downregulated Ki-67 expression. Moreover, stable body weight, normal histological features of major organs, and unaltered blood biochemical parameters were observed in the animals.
Discussion: These findings indicate that Mn-PDA NPs are effective dual-functional agents, serving as both MRI contrast agents and photothermal therapeutics. They exhibit good tumor targeting ability, excellent imaging performance, potent therapeutic efficacy, and high biosafety, thereby offering a promising therapeutic strategy for MPM management.

Keywords: magnetic resonance imaging (MRI); malignant pleural mesothelioma; manganese(II); photothermal therapy (PTT); polydopamine

DOI: https://doi.org/10.3389/fchem.2025.1659283

Ther Adv Med Oncol. 2025 ;17 17588359251378879

Epidemiology and clinical characteristics of mesothelioma in the Chinese population: a multicenter study.

Background: Mesothelioma is a rare and highly aggressive tumor that causes severe damage. However, there is a lack of systematic reports on the incidence and clinical characteristics of mesothelioma in the Chinese population.
Objectives: This study aims to characterize the epidemiological features of mesothelioma in the Chinese population and to evaluate the effectiveness of current treatment strategies, to inform clinical decision-making and improve patient care.
Designs: The epidemiological characteristics of patients were collected by regional study centers according to the predefined inclusion and exclusion criteria. Asbestos exposure status was clearly identified for each patient, and treatment strategies were analyzed across mesothelioma cases with different primary tumor sites.
Methods: Data on mesothelioma patients and their treatment information were collected from 11 hospitals across China between January 2006 and December 2024. Epidemiological data and baseline characteristics were summarized using descriptive methods. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Key response indicators included the objective response rate (ORR) and disease control rate (DCR).
Results: A total of 927 patients from 11 provinces in China were included in the analysis. The major types of mesothelioma observed were pleural mesothelioma (n = 537), peritoneal mesothelioma (n = 240), pericardial mesothelioma (n = 5), and mesothelioma of the tunica vaginalis testis (n = 5). Among these patients, 163 had confirmed asbestos exposure. For pleural mesothelioma, 45.6% (n = 245) of patients were from Yunnan Province. For peritoneal mesothelioma, 62.5% (n = 150) of patients were from Zhejiang Province. The median PFS rates for pleural and peritoneal mesothelioma patients were 6.6 and 5.7 months, respectively. The median OS was 16.6 months for pleural mesothelioma and 12.1 months for peritoneal mesothelioma. The ORR for pleural mesothelioma was 15%, with a DCR of 85.9%, while the ORR for peritoneal mesothelioma was 14.4%, with a DCR of 84.7%.
Conclusion: The incidence of mesothelioma in China exhibits distinct regional characteristics. Pleural mesothelioma is predominantly associated with crocidolite asbestos exposure in Yunnan Province, while peritoneal mesothelioma is linked to hand-spun chrysotile asbestos exposure in Zhejiang Province, with notable sex differences observed. No significant differences in treatment outcomes were identified between pleural and peritoneal mesothelioma patients undergoing first-line therapy. These findings highlight the importance of region-specific strategies for the diagnosis and treatment of mesothelioma in China.

Keywords: asbestos exposure; epidemiology; mesothelioma; pathological types; treatment

DOI: https://doi.org/10.1177/17588359251378879

Transl Oncol. 2025 Sep 30. pii: S1936-5233(25)00287-6. [Epub ahead of print]62 102556

Selective antitumor activity of Tumor Treating Fields (TTFields) involving molecular factors in cancer cells and tumor microenvironment.

Ilaria Fuso Nerini, Rosy Amodeo, Maurizio D'Incalci, Monica Lupi.

The local application of low-intensity electric fields at intermediate frequencies (Tumor Treating Fields - TTFields) has emerged as an effective anticancer treatment in conjunction with chemotherapy and immunotherapy for several solid tumors. Despite this progress, the phenotypic and genetic determinants underlying tumor sensitivity to TTFields remain largely unexplored, representing a critical gap in our understanding. This review provides a comprehensive analysis of preclinical and translational studies describing the cellular factors that influence the anticancer properties of TTFields. An overview of recent omics studies on the complex cellular and molecular processes initiated by TTFields has revealed important mechanisms of action that warrant further investigation for their therapeutic potential. The goal is to identify effects that can be leveraged to develop rational, synergistic co-treatments with anticancer agents that have complementary modes of action. In particular, the ability of TTFields to modulate the tumor microenvironment and reverse the local and systemic immunosuppression could represent a promising strategy to enhance the efficacy of immunotherapy across different tumor types.

Keywords: Anticancer therapy; Preclinical studies; Solid tumors; Tumor Treating Fields (TTFields); Tumor microenvironment

DOI: https://doi.org/10.1016/j.tranon.2025.102556