Malignant Mesothelioma: Time to Translate?

Our plain-English summary of Malignant Mesothelioma: Time to Translate?, by A. Napolitano, M. Carbone (Trends in Cancer, 2016).

The study

• Authors: A. Napolitano, M. Carbone
• Journal: Trends in Cancer
• Published: 2016;2(9):467-474
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is an aggressive cancer largely associated with asbestos exposure. In this review, we will discuss the significant advancements in our understanding of its genetics and molecular biology and their translational relevance. Remarkable findings included the discovery of germline and somatic mutations of BRCA1 associated protein-1 (BAP1) in patients, and the genome-wide characterization of pathways altered in mesothelioma that could be potentially exploited to design novel therapeutic approaches. Nevertheless, the clinical translation of these molecular findings has been slow and insufficient. In order to rapidly move translation from the bench to the bedside, we believe that cooperative research efforts have to be further endorsed and promoted at all levels.

In plain English

This opinion review, not original research, covered mesothelioma genetics, biology and treatment, a cancer the authors describe as largely associated with asbestos exposure. Citing other studies, they reported that about 5% of asbestos miners develop mesothelioma. Inherited BAP1 gene mutations were identified in 2011 in two unrelated American families. They occur in 1–5% of unselected cases, or up to 18–20% after careful clinical selection. Loss of BAP1 protein is reported in over 50% of mesotheliomas. The authors called surgery palliative: no randomized trials support claims it prolongs survival, and the only such trial showed no benefit. In a Phase III trial of patients unable to receive curative surgery, adding bevacizumab to pemetrexed plus cisplatin raised median overall survival from about 16 to about 19 months. Several other drugs, including sunitinib, dasatinib and erlotinib, were stopped early for lack of activity. Vorinostat did not improve overall survival as second- or third-line therapy in the VANTAGE-014 trial. No investigated biomarker is routinely used clinically. The authors concluded that joining forces is the only way to speed laboratory findings into clinical use.

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: Opinion article reviewing published research; no new data were collected
• Who was studied: No study population. The authors reviewed published research on malignant mesothelioma genetics, molecular biology, biomarkers and therapy.
• Exposure: Asbestos, discussed in general terms (described as six commercially used mineral fibers), plus other fibrous minerals such as erionite. No specific exposure was studied.
• Main results:
  • From cited research, not this article's own data: only approximately 5% of asbestos miners develop mesothelioma.
  • From cited research: in 2011, the analysis of two unrelated American families with a high prevalence of mesothelioma led to the identification of BAP1, the first gene whose germline mutations are associated with a higher risk of mesothelioma.
  • From cited research: germline BAP1 mutations are present in only 1–5% of unselected mesothelioma cases, or up to 18–20% of cases after careful clinical selection.
  • From cited research: loss of BAP1 protein has been reported in more than 50% of human mesotheliomas.
  • The authors described surgery as palliative. They said there are no randomized clinical trials supporting the hypothesis that it prolongs survival.
  • From cited research: the only such randomized trial failed to show any benefit of surgery.
  • From a cited Phase III trial: adding bevacizumab to pemetrexed plus cisplatin improved median overall survival from approximately 16 to approximately 19 months in patients with mesothelioma who could not receive curative surgery.
  • From cited research: several drugs, including the tyrosine kinase inhibitors sunitinib, dasatinib and erlotinib, were stopped early in clinical development because of a lack of activity against mesothelioma.
  • From a cited trial: the drug vorinostat failed to improve overall survival as second- or third-line therapy in the VANTAGE-014 trial.
  • None of the putative mesothelioma biomarkers investigated is routinely used in clinical settings.
• The authors' conclusion: The authors concluded that collaboration among research groups (joining forces) is the only way to accelerate the clinical translation of preclinical findings in mesothelioma.

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: Malignant Mesothelioma, Asbestos Exposure, Discovery, Somatic Mutation, BAP1, Mesothelioma.

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