Expression and therapeutic significance of estrogen receptor β in malignant pleural mesothelioma

Our plain-English summary of Expression and therapeutic significance of estrogen receptor β in malignant pleural mesothelioma, by G. Pinton, L. Moro (Future Science OA, 2017).

The study

• Authors: G. Pinton, L. Moro
• Journal: Future Science OA
• Published: 2017;3(2):FSO175
• Type of article: Editorial
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

In plain English

This article was a short commentary in which the authors summarized their own earlier research on estrogen receptor beta (ERβ) in malignant pleural mesothelioma. They described this disease as an asbestos-associated cancer of the pleura. The article reported no new data and did not study asbestos exposure. The authors wrote that their work began from the observation that women with this cancer respond better to treatment and live longer than men. In their earlier study of 78 tumor samples, 2-year survival was 80% for patients whose tumors had high ERβ expression, versus 31% for those with negative or low expression (p = 0.02). None of the 78 samples, and none of the normal pleura, stained positive for estrogen receptor alpha. The authors also summarized earlier cell and animal experiments. In those, activated ERβ reduced mesothelioma cell growth. Separately, re-expressing ERβ in ER-negative cells from biphasic tumors gave those cells a more epithelioid form. An experimental ERβ-activating drug, KB9520, increased the effect of cisplatin/pemetrexed chemotherapy. The authors concluded that drugs selectively targeting ERβ might prove promising for future cancer treatment.

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 summarizing the authors' own previously published studies (tumor sample analysis, gene expression meta-analysis, cell culture and animal experiments); no new data reported
• Who was studied: In the earlier study described: tumor biopsies from 78 malignant pleural mesothelioma patients and normal pleura from healthy controls; a separate meta-analysis of gene expression profiles from 93 mesothelioma samples; mesothelioma cell lines and an animal tumor model
• Exposure: No asbestos exposure was studied. Asbestos is mentioned only as background. The work concerned estrogen receptor beta expression and the ERβ-selective agonist KB9520, alone and with cisplatin/pemetrexed
• Main results:
  • In the earlier 78-sample study, the cumulative probability of survival after 2 years was 80% for patients with high ERβ expression versus 31% for those with negative or low ERβ expression (p = 0.02, log-rank test)
  • None of the 78 mesothelioma biopsies or the normal pleura stained positive for estrogen receptor alpha
  • In earlier cell experiments, ERβ caused a G2-M-phase arrest in mesothelioma cell cycle progression
  • ERβ activated by overexpression or by a selective agonist impaired mitochondrial function in cells, leading to decreased cell proliferation; the effects were also seen in an animal tumor model treated with KB9520
  • Re-expressing ERβ in ER-negative cells from biphasic mesothelioma gave them a more epithelioid phenotype; knocking down ERβ in ER-positive cells gave a more invasive phenotype
  • In hypoxia (low oxygen), the HIF2α to KDM6B pathway induced an epithelioid shape and ERβ expression in biphasic mesothelioma cells that were ER-negative
  • In animals, KB9520 combined with cisplatin/pemetrexed had greater efficacy than either treatment alone. KB9520 had no cytotoxic effect on its own and reduced cisplatin toxicity in non-malignant mesothelial cells expressing ERβ
• The authors' conclusion: The authors concluded that KB9520 may increase the sensitivity of mesothelioma to standard chemotherapy without adding toxicity, and that ERβ-selective drugs might prove promising for developing targeted cancer therapies

Topics

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

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• Estrogen receptor-beta affects the prognosis of human malignant mesothelioma — G. Pinton, E. Brunelli, et al. (2009)
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• Estrogen receptor β activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo — A.G. Manente, D. Valenti, et al. (2013)

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