Malignant mesothelioma resistance to apoptosis: recent discoveries and their implication for effective therapeutic strategies

Our plain-English summary of Malignant mesothelioma resistance to apoptosis: recent discoveries and their implication for effective therapeutic strategies, by F. Villanova, A. Procopio, M.R. Rippo (Current Medicinal Chemistry, 2008).

The study

• Authors: F. Villanova, A. Procopio, M.R. Rippo
• Journal: Current Medicinal Chemistry
• Published: 2008;15(7):631-41
• Type of article: Review
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant Mesothelioma is an aggressive and fatal type of tumor. The incidence of mesothelioma has increased in the past 30 years and is now common as male cancers of the liver, bone and bladder, especially in Europe and Australia. The main risk factor is asbestos exposure even if other co-factor, such as simian virus 40 (SV40) could be implied in its etiology. Unfortunately, its incidence is expected to continue to increase for the next decades, also in rapidly industrializing countries, such as India, where it is not recognised as an occupational disease. Furthermore, some disastrous events, such as the World Trade Center Disaster, may contribute to increase future risk for mesothelioma. The treatment-resistant phenotype of mesothelioma is largely due to its ability to escape from the highly regulated apoptotic machinery. The understanding of the molecular mechanisms responsible of the malignant mesothelioma resistance to apoptosis is now advancing, allowing developing new therapeutic strategies to change the natural history and improve survival of patients. This review gives an overview of the main anti-apoptotic strategies devised by malignant mesothelioma and the therapeutic implication and opportunities for this cancer.

In plain English

This article was a narrative review, not a new study. The authors summarized published research on why malignant mesothelioma resists apoptosis (programmed cell death) and on possible treatments aimed at that resistance. As background, they wrote that more than 80% of mesothelioma cases have been associated with chronic exposure to asbestos fibers. The review covered death receptors (DR4, DR5 and Fas), inhibitor of apoptosis proteins such as XIAP, IAP-1 and survivin, the Bcl-2 protein family, and growth factor signaling (EGF, HGF, VEGF, Wnt and IGF). Most of the work it described was done in cell lines or in animal models. Among the studies it cited, one of 112 mesotheliomas linked high XIAP expression with shorter survival. Another found that blocking IAP-1 made a mesothelioma cell line up to nearly 20-fold more sensitive to cisplatin. The authors noted that DR4 and DR5 antibodies tried in patients with advanced cancer had not been used in mesothelioma patients. The authors concluded that mesothelioma is increasing globally with no known cure. They wrote that these discoveries should make it possible to plan therapies aimed at reversing its resistance to apoptosis.

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 laboratory, animal and clinical research on mesothelioma resistance to apoptosis and related treatment approaches
• Who was studied: no population of its own; the review drew on published studies, mostly of mesothelioma cell lines and animal models, plus some human tumor samples and clinical trials
• Exposure: asbestos exposure was not studied; the introduction gives it as background, describing chrysotile, crocidolite and amosite fibers
• Main results:
  • The review described resistance to apoptosis in mesothelioma cells as due to over-expression of anti-apoptotic proteins such as FLIP, Bcl-2 family members and IAPs, citing other studies
  • A cited study (Kleinberg et al.) of 112 mesotheliomas found XIAP expression higher in peritoneal than pleural mesotheliomas, and high XIAP expression was associated with shorter survival
  • A cited study reported that IAP-1 antisense treatment of a malignant pleural mesothelioma cell line sensitized the cells to cisplatin toxicity up to nearly 20-fold
  • The review cited a report that about 70% of malignant pleural mesotheliomas have high EGFR expression
  • The review noted that antibodies against DR4 and DR5 tested in Phase I and II trials in patients with advanced cancer had not been used in mesothelioma patients
• The authors' conclusion: The authors concluded that malignant mesothelioma is increasing globally and has no known cure. They wrote that recent discoveries on anti-apoptotic mechanisms will make it possible to plan therapies aimed at reverting the apoptosis-resistant phenotype of mesothelioma cells.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Apoptosis, Mesothelioma, Asbestos Exposure, SV40, Etiology, Occupational Disease.

Related studies

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