MTAP Loss and Pleural Mesothelioma (PM): Current Treatment Strategies and Emerging Therapeutic Approaches

Our plain-English summary of MTAP Loss and Pleural Mesothelioma (PM): Current Treatment Strategies and Emerging Therapeutic Approaches, by S. Cedres, L. Masfarre, I. Priano, et al (Cancers, 2026).

The study

• Authors: S. Cedres, L. Masfarre, I. Priano, A. Valdivia, P. Rocha, P. Iranzo, N. Pardo, A. Martinez-Marti, A. Arbusà, L. Cane, M. Soleda, B. Sinigaglia, S. Polo-Alonso, G. Romero-Sola, R. Caro-Consuegra, A. Ortega, E. Felip
• Journal: Cancers
• Published: 2026;18(20)
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

PM is a locally aggressive tumor associated with asbestos exposure. Despite legislative efforts to regulate asbestos use, its incidence continues to rise in some parts of the world. Chemotherapy and immunotherapy have improved survival in PM patients, but overall survival remains poor. MTAP loss is frequent in PM and may influence tumor behavior, resulting in a poorer prognosis. MTAP-deficient tumors exhibit unique metabolic vulnerabilities that have stimulated the development of targeted therapeutic strategies in recent years with promising results. The aim of this review is to analyze the prognostic and predictive value of MTAP in PM patients, as well as the outcomes of drugs with potential activity against this target.

In plain English

This was a review of published research; it created no new data. It summarized studies on loss of the MTAP gene in pleural mesothelioma, a cancer the authors described as associated with asbestos exposure. It reported MTAP deletion in about 40% of pleural mesothelioma patients, and loss of MTAP protein staining in up to 75% of sarcomatoid tumors. Loss of MTAP staining separated mesothelioma from reactive, non-cancerous growths with specificity near 100% but sensitivity of only about 40% to 65%. The authors judged that whether MTAP loss independently predicts shorter survival remained uncertain. Two small immunotherapy studies found no statistically significant outcome differences by MTAP status. Early drug trials included few mesothelioma patients. In an MRTX1719 trial in advanced MTAP-deleted solid tumors, both of the two pleural mesothelioma patients had partial responses. An AMG 193 trial enrolled 80 patients; of its three pleural mesothelioma patients, two had stable disease and one had progressive disease. The authors concluded that MTAP loss is not an established predictive biomarker of immunotherapy resistance, and that results of ongoing trials are needed.

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 research on MTAP loss in pleural mesothelioma (diagnosis, prevalence, prognosis, prediction of treatment response, and targeted therapies)
• Who was studied: No new patients or data; the review drew on previously published laboratory, pathology, genomic and clinical studies of mesothelioma (mainly pleural, some peritoneal)
• Exposure: Not an exposure study. The subject was a tumor genetic change (MTAP loss). Asbestos exposure was mentioned only as the disease's association, and no fiber types or exposure doses were studied.
• Main results:
  • Reviewed studies reported MTAP deletion in about 40% of pleural mesothelioma patients
  • Loss of cytoplasmic MTAP protein staining was reported in about 40% of epithelioid pleural mesotheliomas and in up to 75% of sarcomatoid tumors
  • In the studies cited, loss of MTAP staining distinguished mesothelioma from reactive (non-cancerous) mesothelial proliferations with specificity approaching 100% and sensitivity of about 40% to 65%
  • One retrospective analysis covering multiple tumor types reported median overall survival of 12.8 months for mesotheliomas with MTAP loss versus 23.0 months for MTAP-proficient tumors
  • A Japanese genomic study found MTAP alterations were not independently associated with overall survival; the authors considered the independent prognostic contribution of MTAP uncertain
  • In a study of 22 mesothelioma patients treated with nivolumab, progression-free survival did not differ significantly between those with MTAP loss and those with retained MTAP (4.6 vs. 5.7 months)
  • In a study of 113 patients with pleural or peritoneal mesothelioma, outcomes with nivolumab plus ipilimumab did not differ significantly by MTAP status
  • In an early-phase MRTX1719 study in patients with advanced MTAP-deleted solid tumors, both of the two pleural mesothelioma patients had partial responses
  • The AMG 193 phase I trial enrolled 80 patients with advanced CDKN2A-deleted and/or MTAP-deleted solid tumors, three of them with pleural mesothelioma. Of those three, two had stable disease and one had progressive disease as best response.
  • In preliminary results of the ODM-212 (TEAD inhibitor) study, the response rate in the mesothelioma cohort was 27.8% among the first 18 evaluable patients
  • No therapies had been approved specifically for MTAP-deficient mesothelioma
• The authors' conclusion: The authors concluded that MTAP loss is not currently an established predictive biomarker of immunotherapy resistance or of benefit from TEAD or CDK4/6 inhibitors
• Limitations the authors state:
  • Evidence on predictive value comes mainly from retrospective analyses and from studies of other tumor types
  • Responses to targeted drugs come from very few mesothelioma patients in early-phase trials without long-term follow-up
  • Findings in pleural mesothelioma need separate confirmation in peritoneal mesothelioma
  • Results of ongoing trials are needed to determine whether MTAP-directed therapies work

Topics

Medical terms in this study, explained in our Lexicon: MTAP, Pleural Mesothelioma, Asbestos Exposure, Chemotherapy, Immunotherapy, Overall Survival, Prognosis.

Related studies

• Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies — L. Chiec, D.S. Bruno (2024)
• From biology to therapy: current standards and emerging strategies in pleural mesothelioma — J.H.L.T. van Genugten, C.J. de Gooijer, et al. (2026)
• BAP1 Mutations and Pleural Mesothelioma: Genetic Insights, Clinical Implications, and Therapeutic Perspectives — S. Cedres, A. Valdivia, et al. (2025)
• Increasing the therapeutic index of 5-fluorouracil and 6-thioguanine by targeting loss of MTAP in tumor cells — B. Tang, J.R. Testa, et al. (2012)
• Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review) — D. Andreikos, D.A. Spandidos, et al. (2025)
• Therapeutic vulnerabilities exposed by the 9p21 loss identified through multiparametric drug screening inform rational combination strategies — R. Bevilacqua, P. Gasperini, et al. (2026)

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