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Cancers
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Emerging Concepts in Mesothelioma
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Emerging Concepts in Mesothelioma

A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Clinical Research in Cancer".

Deadline for manuscript submissions: closed (10 June 2026) | Viewed by 3155

Editors

Dr. Georgios T. Stathopoulos

E-Mail Website
Guest Editor
School of Medicine, University of Cyprus, Aglantzia, Nicosia 2109, Cyprus
Interests: biology of lung cancer and mesothelioma; interstitial lung diseases
Dr. Tonia Adamides

E-Mail Website
Guest Editor
Department of Pulmonary Medicine, Nicosia General Hospital, State Health Services Organization, Aglantzia, Nicosia 2100, Cyprus
Interests: biology of lung cancer and mesothelioma; Interstitial lung diseases

Special Issue Information

Dear Colleagues,

Despite extensive research efforts, mesothelioma is still tremendously difficult to treat and mesothelioma incidence rates have not declined significantly despite asbestos bans in more developed countries, while a new incipient and protracted epidemic caused by alternate needle-shaped materials is likely. In these dreadful times, the molecular landscape, the potential treatment strategies, and hopes for the future for patients with mesothelioma are vague. We are pleased to invite you to contribute a piece of certainty to the volatile scenery of mesothelioma diagnosis and treatment in a Special Issued entitled “Emerging Concepts in Mesothelioma”, based on your excellent contributions and involvement in the field.

This Special Issue aims to summarize past understanding and recent progress in mesothelioma research and treatment, and to provide a platform for the guidance of future developments, i.e., molecular profiling, drug screening, patient subgroups and geno/phenotypes, trial design, personalized medicine, etc.

Original research, reviews, and opinion pieces are sought and the involvement of your collaborators and students is welcome. We propose a topic based on your achievements, but this is subject to change. We look forward to receiving your contributions.

Dr. Georgios T. Stathopoulos
Dr. Tonia Adamides
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mesothelioma
  • asbestos
  • pleura
  • tumor suppressor
  • cell lines
  • patient-derived xenograft
  • surgery
  • chemotherapy
  • folate antagonist
  • immunotherapy

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Published Papers (3 papers)

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Research

20 pages, 17564 KB  
Article
Nuclear Factor-κB Signaling in Murine Models of Malignant Pleural Mesothelioma
by Benteng Deng, Ioanna Giopanou, Lori Asarian, Ioannis Lilis, Jianlong Jia, Marina Lianou, Dimitris Simoglou, Giannoula Ntaliarda, Tonia A. Adamide, Isis E. Fernandez and Georgios T. Stathopoulos
Cancers 2026, 18(18), 2990; https://doi.org/10.3390/cancers18182990 - 16 Sep 2026
Viewed by 59
Abstract
Background: Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated cancer in which inflammatory pathways may contribute to tumor behavior. NF-κB signaling is a central mediator of inflammation and cell survival, but the relative contributions of its associated enzymes, IKKα- and IKKβ, in MPM [...] Read more.
Background: Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated cancer in which inflammatory pathways may contribute to tumor behavior. NF-κB signaling is a central mediator of inflammation and cell survival, but the relative contributions of its associated enzymes, IKKα- and IKKβ, in MPM models remain incompletely understood. Methods: We characterized the involvement of IKKα- and IKKβ in tumor formation using several in vitro approaches and the intrapleural or subcutaneous delivery of three murine MPM cell models (AB2, AE17 and KPM1). The experimental approaches included shRNA silencing of Chuk and Ikbkb—the genes encoding the activity of IKKα- and IKKβ—and tumor growth, apoptosis and colony formation measurements. Exploratory pathway and transcriptional analyses were carried out following RNA-sequencing of our murine cell lines and a publicly available human gene expression dataset was also analyzed to provide complementary evidence. Results: Activation of the IKKα- and IKKβ was confirmed in the AB2, AE17 and KPM1 cell lines. Silencing both Chuk and Ikbkb decreased target and cross-target transcripts and metabolic growth. Importantly, Chuk silencing was associated with increased early apoptotic staining in AE17 and KPM1 cells, increased late apoptotic staining in AE17 cells and reduced colony formation in all cell models. Furthermore, Chuk-associated effects on tumor burden and activity were more notable than Ikbkb-associated effects in both intrapleural and subcutaneous tumor formation parameters. Finally, while canonical NF-κB gene-set clustering in both human and murine tumor samples identified specific and shared pathways and transcriptional profiles supporting the in vitro murine assay findings, the analyses remained exploratory and did not specifically establish target dependency. Conclusions: Our data support the involvement of IKK/NF-κB-associated signaling in cell survival, clonogenicity and tumor growth in several MPM murine cell models and identify Chuk-related signaling as a promising target in future studies. Full article
(This article belongs to the Special Issue Emerging Concepts in Mesothelioma)
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22 pages, 2306 KB  
Article
The Diagnostic Trap in Radiation-Induced Mesothelioma: Kinetic-Morphological Decoupling Masks Molecular Aggression
by Norikatsu Fujita, Katsumi Fujita, Hironobu Osumi and Yoshiyasu Takefuji
Cancers 2026, 18(2), 221; https://doi.org/10.3390/cancers18020221 - 9 Jan 2026
Viewed by 1023
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Emerging Concepts in Mesothelioma)
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10 pages, 1144 KB  
Article
Malignant Local Seeding in Procedure Tracts of Pleural Mesothelioma: Incidence and Novel Risk Factors in 308 Patients
by Moshe Lapidot, Emanuele Mazzola and Raphael Bueno
Cancers 2025, 17(17), 2786; https://doi.org/10.3390/cancers17172786 - 26 Aug 2025
Cited by 5 | Viewed by 1361
Abstract
Background/Objectives: Unlike other thoracic malignancies, seeding malignant cells along surgical tracts is a known complication of invasive diagnostic or therapeutic procedures for pleural mesothelioma (PM). We report the tract dissemination rate and risk factors in 308 consecutive patients treated over 9 years [...] Read more.
Background/Objectives: Unlike other thoracic malignancies, seeding malignant cells along surgical tracts is a known complication of invasive diagnostic or therapeutic procedures for pleural mesothelioma (PM). We report the tract dissemination rate and risk factors in 308 consecutive patients treated over 9 years in a single institution who underwent pleurectomy decortication (PD). Methods: Clinical and outcome data were reviewed. Fisher’s exact test, Kaplan–Meier estimators, and log-rank tests were used to identify significant risk factors for surgical tract dissemination and to compare overall survival. Results: There were 233 males (75.6%), 187 right-sided operations (61%), 190 (61.7%) epithelioid histology cases, and the median age was 69 (29–84). During the study, malignant cell dissemination in resected surgical tracts was diagnosed in 69 (22.4%) patients. The dissemination rates in epithelioid, biphasic, and sarcomatoid tumors were 24.7%, 20.4%, and 0%, respectively. Disseminated malignant surgical tract was associated with advanced nodal status (p = 0.001), advanced staging by the American Joint Committee on Cancer (AJCC 8th edition, p = 0.03), female sex (0.02), side of surgery (p = 0.03), and the number of video-assisted thoracoscopic surgery (VATS) ports (p = 0.003). In epithelioid mesothelioma, the median survival from diagnosis was 19.7 months in patients with tract seeding versus 36.3 months in patients without seeding (hazard ratio, 1.9; p = 0.001). Conclusions: Procedure tract dissemination occurs in almost every fourth patient with pleural mesothelioma and is associated with shorter overall survival in the epithelioid subtype. Full article
(This article belongs to the Special Issue Emerging Concepts in Mesothelioma)
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