New vistas in malignant mesothelioma: MicroRNA architecture and NRF2/MAPK signal transduction

Our plain-English summary of New vistas in malignant mesothelioma: MicroRNA architecture and NRF2/MAPK signal transduction, by M. Gandhi, S. Nair (Life Sciences, 2020).

The study

• Authors: M. Gandhi, S. Nair
• Journal: Life Sciences
• Published: 2020;257:118123
• Type of article: Review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is a cancer of the mesothelial lining of the pleura, peritoneum, pericardium and testes. The most common form is asbestos-linked MM that is etiologically linked to repeated asbestos exposure with a long latency period, although non-asbestos MM has also been reported. Late diagnosis, poor survival rates, lack of diagnostic and prognostic markers act as major impediments in the clinical management of MM. Despite advances in immune checkpoint inhibition and CAR T-cell-based therapies, MM which is of different histologic subtypes remains challenging to treat. We review microRNAs (miRNAs) and the miRNA interactome implicated in MM which can be useful as circulating miRNA biomarkers for early diagnosis of MM and as biomarkers for prognostication in MM. Further, we underscore the relevance of the NRF2/MAPK signal transduction pathway that has been implicated in MM which may be useful as druggable targets or as biomarkers of predictive response. In addition, since MM is driven partly by inflammation, we elucidate chemopreventive phytochemicals that are beneficial in MM, either via crosstalk with the NRF2/MAPK pathway or via concerted anticancer mechanisms, and may be of benefit as adjuvants in chemotherapy. Taken together, a multifactorial approach comprising identification of miRNA target hubs and NRF2/MAPK biomarkers along with appropriately designed clinical trials may enable early detection and faster intervention in MM translating into better patient outcomes for this aggressive cancer.

Copyright © 2020 Elsevier Inc. All rights reserved.

In plain English

This review did not study new patients or workers. The authors gathered published clinical and laboratory studies on malignant mesothelioma. They describe its most common form as linked to repeated asbestos exposure, while noting that non-asbestos mesothelioma has also been reported. They focused on two topics. The first was microRNAs, small RNA molecules that may serve as disease markers in blood, fluid or tissue. The second was a group of cell signaling pathways called NRF2/MAPK. They also listed registered mesothelioma clinical trials. Using computer tools, the authors mapped predicted interactions among microRNAs reported as raised or lowered in mesothelioma. One reviewed study was a nested case-control study of 17 male mesothelioma patients from a cohort of 2769 German workers. It tested blood samples taken a median 8.9 months before diagnosis. Three microRNAs showed practically nil (0%) sensitivity for early detection, with 98% specificity. The authors noted that only two clinical studies had targeted NRF2/MAPK, and that clinical use of microRNA markers was still evolving. The authors concluded that combining microRNA and NRF2/MAPK markers with appropriately designed clinical trials may help earlier detection of mesothelioma.

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 clinical and preclinical studies and registered clinical trials, with the authors' own computer-based (in silico) network analysis of reported microRNAs
• Who was studied: Published clinical and pre-clinical reports on malignant mesothelioma (patient samples, cell lines, mouse models), plus clinical trials listed in the NIH Clinical Trials Registry
• Exposure: Not an exposure study. The review describes the most common form of mesothelioma as asbestos-linked, related to repeated asbestos exposure, and notes that non-asbestos mesothelioma has also been reported. Its subject is microRNAs and NRF2/MAPK signaling, not asbestos exposure levels.
• Main results:
  • The authors' predicted interaction network of microRNAs reported as upregulated in mesothelioma had 77 nodes and 2926 edges
  • The authors' predicted interaction network of microRNAs reported as downregulated in mesothelioma had 164 nodes and 13,366 edges
  • A cited nested case-control study by Weber et al. tested the blood microRNAs miR-103a-3p, miR-126-3p and miR-132-3p in prediagnostic plasma samples, taken a median 8.9 months before clinical diagnosis. The samples came from 17 male mesothelioma patients drawn from a cohort of 2769 German workers. The markers showed practically nil (0%) sensitivity, with 98% specificity.
  • The authors reported that only two clinical studies had targeted the NRF2/MAPK pathway in mesothelioma: NCT01938443 (trametinib) and NCT00996567 (cetuximab)
• The authors' conclusion: The authors speculated that a combined strategy may be useful for earlier detection and better prognosis of mesothelioma. That strategy would evaluate circulating microRNAs and microRNA network hubs together with NRF2/MAPK pathway biomarkers, alongside tailored clinical trials.
• Limitations the authors state:
  • The authors stated that clinical adoption of microRNAs for diagnosis or prognosis of mesothelioma is still evolving and needs more work before routine clinical use
  • The authors noted that most of the mesothelioma clinical trials they listed are in early phases of clinical research

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, Pleura, Peritoneum, Pericardium, Asbestos Exposure, Latency, Histological Subtype, Biomarker.

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