Cyclooxygenase-2, epidermal growth factor receptor, and aromatase signaling in inflammation and mesothelioma

Our plain-English summary of Cyclooxygenase-2, epidermal growth factor receptor, and aromatase signaling in inflammation and mesothelioma, by B. Nuvoli, R. Galati (Molecular Cancer Therapeutics, 2013).

The study

• Authors: B. Nuvoli, R. Galati
• Journal: Molecular Cancer Therapeutics
• Published: 2013;12(6):844-52
• Type of article: Review
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma or mesothelioma is a rare form of cancer that develops from transformed cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is directly linked to asbestos exposure, which acts as a carcinogen by initiating the carcinogenic process. Because of their shape, asbestos fibers can cross the membrane barriers inside the body and cause inflammatory and fibrotic reactions. Such reactions are believed to be the mechanism by which asbestos fibers may trigger malignant mesothelioma in the pleural membrane around the lungs. Carcinogens are known to modulate the transcription factors, antiapoptotic proteins, proapoptotic proteins, protein kinases, cell-cycle proteins, cell adhesion molecules, COX-2, and growth factor signaling pathways. This article reviews recent studies regarding some malignant mesothelioma molecular targets not only for cancer prevention but also for cancer therapy.

©2013 AACR

In plain English

This article was a review rather than an original study. The authors reviewed published laboratory and clinical research on three molecules in malignant mesothelioma: the enzyme COX-2, the epidermal growth factor receptor (EGFR), and the enzyme aromatase (CYP19A1), and on how these may link inflammation to the disease. The article described insoluble amphibole fibers as causing a chronic inflammatory state. Among the earlier studies it cited, one reported that COX-2 expression was a strong prognostic factor in human mesothelioma. Another found EGFR overexpression in 52% of epithelial malignant mesothelioma. A third, a study of malignant peritoneal mesothelioma, found EGFR mutations in 31% (9/29) of cases. Earlier work found CYP19A1 in most mesothelioma samples, with its cytoplasmic expression significantly correlated with poor survival. The same work found that the aromatase inhibitor exemestane reduced the growth of mesothelioma cells in the laboratory. The authors noted that no clinical trials of aromatase inhibitors in mesothelioma were under way. They concluded that these markers were still under investigation, needed validation in larger prospective studies, and could be targeted for prevention and therapy.

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 studies. No literature search method is described.
• Who was studied: No study population of its own. The review drew on published laboratory, tissue and clinical studies of malignant mesothelioma, plus a table of clinical trials of COX-2, EGFR and CYP19A1 inhibitors.
• Exposure: Asbestos exposure was not measured. The review discusses asbestos fibers in general, and insoluble amphibole fibers, as triggers of chronic inflammation leading to mesothelioma.
• Main results:
  • A cited earlier study (not this review) reported that COX-2 expression was a strong prognostic factor in human mesothelioma.
  • A cited earlier study found EGFR overexpression by immunohistochemistry in 52% of epithelial malignant mesothelioma, and reported it as a factor negatively affecting prognosis.
  • A cited earlier study found EGFR mutations in 31% (9/29) of malignant mesothelioma cases. The reference list identifies it as a study of malignant peritoneal mesothelioma (reference 55, Foster and colleagues).
  • A cited earlier laboratory study observed a synergistic effect of gefitinib (an EGFR inhibitor) and rofecoxib (a COX-2 inhibitor) on mesothelioma cell death.
  • Cited earlier work found CYP19A1 expressed in the majority of samples from patients with malignant mesothelioma, and found its cytoplasmic expression significantly correlated with poor survival.
  • In cited laboratory work, treating mesothelioma cells with exemestane, an aromatase inhibitor, led to significant reduction of tumor cell growth.
  • A cited study of environmental asbestos exposure in a rural area of Anatolia, Turkey, found the risk of malignant mesothelioma was higher in women than in men.
  • The authors stated that no clinical trials of CYP19A1 inhibitors in malignant mesothelioma were being conducted at the time.
• The authors' conclusion: The authors concluded that COX-2, EGFR and CYP19A1 were still under investigation. They wrote that the molecules and pathways connecting chronic inflammation with cancer formation could be targeted by drugs or natural products for new preventive and treatment strategies for malignant mesothelioma.
• Limitations the authors state:
  • The authors stated that the cross-talk between these markers and their value as prognostic indicators will need to be validated in prospective studies in larger patient populations.
  • The authors noted that earlier reports of EGFR expression in mesothelioma gave controversial results, possibly because there was no standardized method of EGFR detection.

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: Inflammation, Mesothelioma, Malignant Mesothelioma, Mesothelium, Asbestos Exposure, Carcinogenic.

Related studies

• Asbestos-induced phosphorylation of epidermal growth factor receptor is linked to c-fos and apoptosis — C.L. Zanella, C.R. Timblin, et al. (1999)
• Malignant pleural mesothelioma and epidermal growth factor receptor (EGF-R). Relationship of EGF-R with histology and survival using fixed paraffin embedded tissue and the F4, monoclonal antibody — H. Dazzi, P.S. Hasleton, et al. (1990)
• Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers — J.C. Pache, Y.M. Janssen, et al. (1998)
• Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres — S.P. Faux, C.E. Houghton, et al. (2000)
• Targeted epidermal growth factor receptor therapy in malignant pleural mesothelioma: where do we stand? — V. Agarwal, M.J. Lind, et al. (2011)
• Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations — O. Rena, L.R. Boldorini, et al. (2011)

Browse more research in Molecular Cancer Therapeutics, or return to medical research.