Advances in the biology of malignant pleural mesothelioma

Our plain-English summary of Advances in the biology of malignant pleural mesothelioma, by P.A. Zucali, G.L. Ceresoli, F. De Vincenzo, et al (Cancer Treatment Reviews, 2011).

The study

• Authors: P.A. Zucali, G.L. Ceresoli, F. De Vincenzo, M. Simonelli, E. Lorenzi, L. Gianoncelli, A. Santoro
• Journal: Cancer Treatment Reviews
• Published: 2011;37(7):543-58
• Type of article: Review
• Cited by: 81 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is a highly aggressive cancer with a very poor prognosis. Although the mechanism of carcinogenesis is not fully understood, approximately 80% of malignant pleural mesothelioma can be attributed to asbestos fiber exposure. This disease is largely unresponsive to conventional chemotherapy or radiotherapy, and most patients die within 10-17 months of their first symptoms. Currently, malignant pleural mesothelioma therapy is guided by clinical stage and patient characteristics rather than by the histological or molecular features of the tumor. Several molecular pathways involved in malignant pleural mesothelioma have been identified; these include cell cycle regulation, apoptosis, growth factor pathways, and angiogenesis. Unfortunately, several agents targeting these processes, including erlotinib, gefitinib, and imatinib, have proven ineffective in clinical trials. A greater understanding of the molecular pathways involved in malignant pleural mesothelioma is needed to develop better diagnostics, therapeutics, and preventative measures. Moreover, understanding the biological basis of mesothelioma progression may facilitate personalized treatment approaches, and early identification of poor prognostic indicators may help reduce the heterogeneity of the clinical response. This paper reviews advances in the molecular biology of malignant pleural mesothelioma in terms of pathogenesis, the major molecular pathways and the associated therapeutic strategies, and the roles of biomarkers.

Copyright © 2011 Elsevier Ltd. All rights reserved.

In plain English

This article was a review, not a new study. The authors searched PubMed and Cancerlit, reference lists, meeting abstracts and clinicaltrials.gov. They summarized research on the biology of malignant pleural mesothelioma: how it develops, the molecular pathways involved, related drug treatments, and biomarkers. The review stated that approximately 80% of malignant pleural mesothelioma can be attributed to asbestos fiber exposure. It gave the latency from first exposure to diagnosis as about 30 years, ranging from 20 to 50 years. It said crocidolite is considered the most oncogenic type of asbestos and described the role of the SV40 virus as controversial. Citing earlier trials, it reported minimal activity for gefitinib and erlotinib and no responses to imatinib. In one cited study, median survival was 10 months for pleural mesotheliomas with p16 deletion versus 34 months for those without. The authors concluded that no single "magic bullet" should be expected. They wrote that better understanding of the disease's molecular changes should help identify biomarkers and new treatments.

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 literature review
• Who was studied: Published literature on malignant pleural mesothelioma found through PubMed and Cancerlit, manual searches of reference lists, abstracts from ASCO, ESMO, IASLC and IMIG meetings, and ongoing trials listed on clinicaltrials.gov; no search dates or number of included studies are given
• Exposure: Asbestos (serpentine chrysotile and amphiboles: crocidolite, amosite, anthophyllite, actinolite, tremolite), plus SV40 virus, radiation and erionite as other potential causes; the review states about 80% of MPM can be attributed to asbestos
• Main results:
  • The review gives the latency between initial asbestos exposure and diagnosis as about 30 years, ranging from 20 to 50 years
  • The review states that the link between amphibole asbestos exposure and MPM is generally accepted and that crocidolite is considered the most oncogenic type of asbestos
  • The review describes the role of SV40 virus in mesothelioma as controversial
  • Citing earlier trials in MPM patients, the review reports minimal activity of gefitinib (two phase II trials) and erlotinib (one trial)
  • Citing four phase II trials, the review reports that imatinib achieved no responses in untreated or pre-treated patients
  • In a cited microarray analysis of 99 mesothelioma specimens, median survival in pleural mesotheliomas was 10 months for p16-deleted cases versus 34 months for non-deleted cases (P = 0.001)
  • In a cited study of 66 mesothelioma patients, 20 healthy controls and 81 others, sensitivity for detecting mesothelioma at 95% specificity was 34% for MPF, 47% for osteopontin and 73% for SMRP; combining them did not improve sensitivity
  • In a cited animal experiment, mesothelioma occurred in 40 of 40 (100%) rats injected with erionite, compared with 19 of 40 (48%) rats injected with asbestos
• The authors' conclusion: The authors concluded that malignant mesothelioma is likely the result of multiple genetic alterations built up over many years and that no single "magic bullet" should be expected. They wrote that better understanding of its molecular alterations should help identify predictive or prognostic biomarkers and develop new treatments, possibly targeted agents combined with chemotherapy, and that individually tailored treatments will offer better outcomes in the future.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Carcinogenesis, Chemotherapy, Apoptosis, Angiogenesis, Clinical Trial, Mesothelioma.

Related studies

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• Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2011)
• Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma — P.A. Zucali, M. Perrino, et al. (2014)
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• BAP1 Immunostain and CDKN2A (p16) FISH Analysis: Clinical Applicability for the Diagnosis of Malignant Mesothelioma in Effusions — A.E. Walts, K. Hiroshima, et al. (2016)

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