Clinical Importance of Molecular Biomarkers in Pleural Mesothelioma

Our plain-English summary of Clinical Importance of Molecular Biomarkers in Pleural Mesothelioma, by L. Roof, K. Koehler, C. Verschraegen (Cancers, 2026).

The study

• Authors: L. Roof, K. Koehler, C. Verschraegen
• Journal: Cancers
• Published: 2026;18(4)
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is a rare malignancy with opportunities for improvement in current treatment paradigms despite recent advances in systemic therapy. While histology remains the most clinically relevant prognostic indicator, the expanding use of immunotherapy and ongoing clinical trials involving targeted therapies have increased interest in the development of predictive and prognostic biomarkers in this disease. This review summarizes the current biologic and therapeutic landscape of PM and the biomarkers that influence prognosis and treatment response. Biomarkers such as programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) demonstrate inconsistent predictive value in PM and are not currently used in clinical decision pathways in the real-world setting. This review highlights the developing role of dynamic biomarkers such as circulating tumor DNA (ctDNA) for molecular response assessment and minimal residual disease (MRD) detection. This review also examines important genomic and transcriptomic alterations in PM, such as MTAP, BAP1, CDKN2A, and NF2/YAP/TEAD. These alterations provide potential targets for ongoing early-phase clinical trials. Future advances in PM will depend on the development and integration of comprehensive biomarker models that combine clinicopathologic, immune, and molecular features of this complex and heterogenous disease.

In plain English

This was a review of published studies and trials; the authors analyzed no new data. It covered biomarkers (measurable tumor or blood features) in pleural mesothelioma, for which the authors called asbestos exposure the most important risk factor. The authors reported that tumor histology (cell type) remained the most clinically relevant factor for prognosis and treatment choice, while PD-L1 and tumor mutational burden had inconsistent predictive value. They described exploratory analyses from a phase 2 trial of perioperative nivolumab with or without ipilimumab in resectable pleural mesothelioma: 13 of 25 patients had detectable tumor DNA in the blood before surgery, and those without it had a median progression-free survival of 23.26 months versus 2.46 months for those with it. Citing other studies, they reported MTAP loss in approximately 40–60% of cases, sporadic BAP1 loss in about half, and NF2 loss in approximately 30–50%. The authors concluded that some known factors help predict survival but none had been shown to prolong survival meaningfully, noting that much of the evidence came from retrospective analyses of tumor specimens.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature and ongoing clinical trials; no new data
• Who was studied: Published studies and clinical trials (completed and ongoing) on biomarkers in pleural mesothelioma; no patients were studied directly
• Exposure: The review did not study an asbestos exposure. It examined tumor and blood biomarkers (histology, PD-L1, tumor mutational burden, circulating tumor DNA, MTAP, BAP1, CDKN2A, NF2/YAP/TEAD, tumor microenvironment, miRNAs). It described asbestos exposure as the most important risk factor for pleural mesothelioma.
• Main results:
  • Based on the reviewed literature, histology (epithelioid, sarcomatoid, biphasic) remained the most clinically relevant factor for prognosis and for choosing systemic therapy
  • PD-L1 and tumor mutational burden (TMB) had shown inconsistent value for predicting treatment response in pleural mesothelioma
  • A cited phase 2 trial of perioperative nivolumab versus nivolumab plus ipilimumab in resectable pleural mesothelioma (Reuss et al.) reported exploratory analyses of tumor-informed circulating tumor DNA (ctDNA) assays
  • In that trial, 13 of 25 patients (52%) had detectable ctDNA preoperatively
  • In that trial, patients with undetectable ctDNA at the preoperative timepoint had a median progression-free survival of 23.26 months, versus 2.46 months for patients with detectable ctDNA (log-rank p = 0.0059; HR = 0.29, 95% CI 0.12–0.73)
  • From cited genomic studies: MTAP loss occurs in approximately 40–60% of pleural mesothelioma, with higher rates in non-epithelioid histologies
  • From cited studies: BAP1 is lost sporadically in approximately half of cases, and germline loss occurs in 5% of cases
  • From cited studies: NF2 loss of function occurs in approximately 30–50% of pleural mesothelioma cases
  • Many early-phase clinical trials of targeted therapies in pleural mesothelioma were ongoing, but biomarker-driven treatment remained limited in clinical practice
• The authors' conclusion: The authors concluded that some known factors help predict survival in pleural mesothelioma, but none have been shown to prolong survival in a meaningful way
• Limitations the authors state:
  • The authors stated that much of the available evidence consists of retrospective analyses of tumor specimens, small translational cohorts and exploratory analyses within early-phase studies
  • The authors stated that the field lacks prospectively validated predictive models and standardized assays
  • The authors stated that because the disease is rare, it is difficult to gather enough tumor specimens for research

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Systemic Therapy, Histology, Immunotherapy, Clinical Trial, Prognosis, PD-L1.

Related studies

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• The Importance of Multidisciplinary Approach in Early Detection of BAP1 Tumor Predisposition Syndrome: Clinical Management and Risk Assessment — A. Battaglia (2014)
• The relative importance of clinical, radiological and pulmonary function variables in evaluating asbestosis and chronic obstructive airway disease in asbestos workers — G.M. Regan, B. Tagg, et al. (1971)
• Expression Profile of Sphingosine Kinase 1 Isoforms in Human Cancer Tissues and Cells: Importance and Clinical Relevance of the Neglected 1b-Isoform — H. Chen, N. Haddadi, et al. (2022)
• Molecular biomarkers in malignant mesothelioma: state of the art — S.C. Kao, G. Reid, et al. (2011)
• Editorial: Moving beyond the molecular mechanisms of malignant pleural mesothelioma: Cues for novel biomarkers and drug targets — I. Cavallari, F. Cerciello, et al. (2023)

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