Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review)

Our plain-English summary of Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review), by D. Andreikos, D.A. Spandidos, V.E. Georgakopoulou (International Journal of Oncology, 2025).

The study

• Authors: D. Andreikos, D.A. Spandidos, V.E. Georgakopoulou
• Journal: International Journal of Oncology
• Published: 2025;66(3)
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare but aggressive cancer linked to asbestos exposure and characterized by advanced‑stage disease at presentation. Despite advances in treatment, prognosis remains abysmal, highlighting the imperative for the development of novel biomarkers and treatment approaches. Telomere biology plays a pivotal role in the tumorigenic process and has emerged as a key area in oncology research. Short telomeres have been associated with genomic instability, and substantially shorter telomere length (TL) has been identified in MM, showcasing the potential of TL in risk assessment, early detection, and disease progression monitoring. MM predominantly maintains TL through telomerase activity (TA), which in research has been identified in >90% of MM cases, underscoring the potential of TA as a biomarker in MM. Telomerase reverse transcriptase (TERT) polymorphisms may serve as valuable biomarkers, with research identifying associations between single nucleotide polymorphisms (SNPs) and the risk and prognosis of MM. Additionally, TERT promoter mutations have been associated with poor prognosis and advanced‑stage disease, with the non‑canonical functions of TERT hypothesized to contribute to the development of MM. TERT promoter mutations occur in ~12% of MM cases; C228T, C250T and A161C are the most common, while the distribution and frequency differ depending on histological subtype. Research reveals the promise of the various approaches therapeutically targeting telomerase, with favorable results in pre‑clinical models and inconclusive findings in clinical trials. The present review examines the role of telomere biology in MM and its implications in diagnosis, prognosis, and therapy.

In plain English

This article was a review, not a new study. The authors summarised published research on telomeres (the protective ends of chromosomes) and telomerase (the enzyme that maintains them) in malignant mesothelioma (MM). One study they described reported shorter telomeres in asbestos-exposed people without MM than in non-exposed people (P=0.047). Cited studies found telomerase activity in 91 to 100% of MM, which the authors described as pleural mesothelioma, compared with 63.6% of diffuse malignant peritoneal mesothelioma cases in one study. Mutations in the promoter region of the TERT gene were reported in about 12% of MM cases. In one cited study these mutations were more frequent in nonepithelioid than in epithelioid MM (22.2% vs. 5.5%), and median overall survival was 262 days with the mutation versus 469 days without it. A telomerase-targeting virus treatment gave favourable results in mice. A phase II trial of the UV1 telomerase vaccine did not meet its primary goal. The authors concluded that telomere shortening may serve as a marker for early detection and risk assessment but that its prognostic role remains inconclusive. They called for larger studies.

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 laboratory, animal and clinical studies on telomere biology in malignant mesothelioma
• Who was studied: No study population of its own; the review drew on previously published studies of malignant mesothelioma tumors, cell lines, pleural effusions, mouse models and clinical trials
• Exposure: Not an exposure study. The review describes asbestos exposure as the main risk factor for MM and discusses telomere length in asbestos-exposed people; its focus is telomere length, telomerase activity, TERT gene variants and telomerase-targeted treatments
• Main results:
  • In a cited study (Aida et al), telomere length was shorter in asbestos-exposed individuals without MM than in non-exposed individuals (P=0.047)
  • Across cited studies, telomerase activity was found in 91 to 100% of MM, with the alternative lengthening of telomeres (ALT) mechanism absent or rare; the authors state that pleural MMs are overwhelmingly telomerase-positive and ALT-negative
  • In diffuse malignant peritoneal mesothelioma (DMPM), a cited study found telomerase activity in 63.6% of cases and ALT in 18%
  • In the largest cited study (266 MM tumors), TERT promoter mutations were found with a frequency of 12%
  • In a cited study (Pirker et al), TERT promoter mutation frequency was 22.2% in nonepithelioid MM vs. 5.5% in epithelioid MM (P<0.001)
  • In the same cited study, median overall survival was 262 days in TERT promoter-mutated cases vs. 469 days in wild-type cases (P<0.0001)
  • In a cited study (Quetel et al), TERT promoter mutations were more frequent in patients with stage IV tumors (28%) than in patients with stage I/III tumors (13%) (P=0.007)
  • In a cited study (Mervic et al), the TERT rs10069690 TT genotype was associated with higher MM risk after age adjustment (OR 2.22, 95% CI 1.10 to 4.48)
  • In a cited mouse experiment, 71.4% of mice given the telomerase-specific virus OBP-301 combined with a heparinase-expressing virus were alive at 12 weeks, compared with 14.3% given OBP-301 alone
  • In the NIPU phase II trial of the UV1 telomerase vaccine added to nivolumab and ipilimumab, the primary endpoint (improved progression-free survival by blinded independent review) was not achieved
• The authors' conclusion: The authors concluded that telomere shortening seen in MM may serve as a biomarker for early detection and risk assessment, especially in asbestos-exposed people, but that its role as a prognostic biomarker remains inconclusive; they described results of telomerase vaccines as encouraging but said caution is needed
• Limitations the authors state:
  • The authors state that small cohort sizes in many of the studies reviewed call for larger prospective studies
  • The authors state that the evidence on TERT promoter mutations may be limited by the retrospective design and the sample sizes of the studies

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Biomarker, Malignant Mesothelioma, Asbestos Exposure, Prognosis, Disease Progression, Histological Subtype, Clinical Trial.

Related studies

• Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases — A. Mervic, K. Goricar, et al. (2024)
• Measurement of telomere length in cells from pleural effusion: Asbestos exposure causes telomere shortening in pleural mesothelial cells — S. Aida, J. Aida, et al. (2018)
• Telomerase activity in human pleural mesothelioma — K. Dhaene, R. Hübner, et al. (1998)
• Telomerase activity analyzed with TRAP in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis — E. Adell, A. Dejmek (2014)
• SV40 infection induces telomerase activity in human mesothelial cells — R. Foddis, A. De Rienzo, et al. (2002)
• Telomerase activity in pleural malignant mesotheliomas — A.Y. Au, T. Hackl, et al. (2011)

Browse more research in International Journal of Oncology, or return to medical research.