Precision Therapy for Mesothelioma: Feasibility and New Opportunities

Our plain-English summary of Precision Therapy for Mesothelioma: Feasibility and New Opportunities, by S. Dulloo, A. Bzura, D.A. Fennell (Cancers, 2021).

The study

• Authors: S. Dulloo, A. Bzura, D.A. Fennell
• Journal: Cancers
• Published: 2021;13(10)
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesotheliomas (MPMs) are characterised by their wide variation in natural history, ranging from minimally to highly aggressive, associated with both interpatient and intra-tumour genomic heterogeneity. Recent insights into the nature of this genetic variation, the identification of drivers, and the emergence of novel strategies capable of targeting vulnerabilities that result from the inactivation of key tumour suppressors suggest that new approaches to molecularly strategy therapy for mesothelioma may be feasible.

In plain English

This article was a commentary, not an original study. The authors reviewed published research and ongoing trials of targeted ('precision') treatments for mesothelioma, mostly malignant pleural mesothelioma, aimed at specific genetic changes in tumours. Topics included tumour type (epithelioid, biphasic, sarcomatoid) and changes in NF2 and the Hippo pathway, BAP1, the 9p21.3 region (CDKN2A, MTAP), ALK and PTCH1. These included the ADAM trial of ADI-PEG20, which reported a hazard ratio of 0.56 for progression-free survival against best supportive care. A tazemetostat study enrolled 74 patients with BAP1-inactivated mesothelioma and reported 51% disease control at 12 weeks. The MiST1 trial of rucaparib, in patients with BAP1- or BRCA1-deficient mesothelioma, reported 58% disease control at 12 weeks (95% CI 37 to 77). The COMMAND trial of defactinib was negative. The authors described ALK rearrangement as more common in peritoneal than in pleural mesothelioma. The article did not study asbestos exposure. The authors concluded that targeted therapy for mesothelioma is in its infancy, but that promising developments suggest it may be feasible for the more common genetic changes.

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: Commentary (narrative review of published studies and ongoing clinical trials; no new data)
• Who was studied: No study population of its own. The commentary discussed published research and trials on malignant pleural mesothelioma and, for some topics, peritoneal mesothelioma.
• Exposure: Not an exposure study. The subject was drug treatments targeting genetic alterations in mesothelioma tumours. Asbestos is mentioned only in the conclusion, as a reason mesothelioma will remain a global health issue.
• Main results:
  • Reported from the cited ADAM trial (ADI-PEG20 versus best supportive care): the primary endpoint was progression-free survival, and the trial met it with a hazard ratio of 0.56.
  • Reported from a cited phase 1 study of ADI-PEG 20 with pemetrexed and cisplatin: 7 of 9 MPM patients (78%) had partial responses.
  • Reported from a cited study of tazemetostat in patients with BAP1-inactivated mesothelioma: 74 patients enrolled. 51% had disease control at 12 weeks, and 25% continued to 24 weeks.
  • Reported from the cited MiST1 trial of rucaparib in patients with BAP1- or BRCA1-deficient mesothelioma: the 12-week disease control rate was 58% (95% CI 37 to 77).
  • Reported from the cited COMMAND trial (maintenance defactinib versus placebo, merlin-stratified): the trial was negative.
  • Reported from a cited study of pleural MPM: 25 of 128 patients (19.5%) had overexpressed ALK transcripts. The authors stated that ALK rearrangement tends to be more prevalent in peritoneal mesothelioma.
• The authors' conclusion: The authors concluded that targeted therapy for mesothelioma is in its infancy. In their view, targeting altered tumour suppressors remains a challenge, but promising developments suggest it may be feasible for the more common genetic alterations.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma.

Related studies

• Advances in Precision Oncology: Targeted Thorium-227 Conjugates As a New Modality in Targeted Alpha Therapy — U.B. Hagemann, K. Wickstroem, et al. (2020)
• Targeted Therapy Recommendations for Therapy Refractory Solid Tumors-Data from the Real-World Precision Medicine Platform MONDTI — H. Taghizadeh, M. Unseld, et al. (2020)
• DNA methylation status classifies pleural mesothelioma cells according to their immune profile: implication for precision epigenetic therapy — M.F. Lofiego, R. Tufano, et al. (2025)
• Multi-omics integration in malignant pleural mesothelioma: from molecular evolution and immune ecosystems to precision therapy — H. Li, K. Zhou, et al. (2026)
• A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma — B.C. Cho, R. Feld, et al. (2014)
• Local Cancer Recurrence: The Realities, Challenges, and Opportunities for New Therapies — D.A. Mahvi, R. Liu, et al. (2018)

Browse more research in Cancers, or return to medical research.