Advances in malignant pleural mesothelioma therapy: targeting EphA2 a novel approach

Our plain-English summary of Advances in malignant pleural mesothelioma therapy: targeting EphA2 a novel approach, by N. Nasreen, N. Khodayari, K.A. Mohammed (American Journal of Cancer Research, 2012).

The study

• Authors: N. Nasreen, N. Khodayari, K.A. Mohammed
• Journal: American Journal of Cancer Research
• Published: 2012;2(2):222-34
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with a poor prognosis. MPM grows from the mesothelial cells lining the surface of the lung and chest wall called Pleura. Exposure to asbestos is mainly linked to the development of MPM. Approximately 80% of the tumors are pleural in origin, and up to 3000 people are diagnosed with MPM in the United States annually. The incidence of MPM is expected to rise in the coming decades particularly in the developing countries. Although there is an increase in the awareness of danger associated with the use of asbestos, its use is still prevalent in Australia and Asia because of its durability and low cost. This further warns and adds to the mortality and morbidity of patients with MPM globally. The traditional treatment strategies have shown only modest improvement towards the disease. MPM is difficult to treat because of the fact that the time between the exposure to asbestos and the appearance of symptoms is extremely delayed, and also due to tumor involvement with the pleural surface and the adjoining tissues such as the chest wall, pericardium and sub-diaphragmatic organs. Despite advances in the diagnostic and treatment approaches the median survival rate for MPM is between 9 to 17 months. The standard care with double agent has shown modest improvement however, multimodality approach using novel targets may have potential to achieve the improvement in the survival rate. In this review we give an update on the conventional treatment modalities and discuss about various molecular targets including receptor EphA2, a novel target gene which may be considered as a biomarker for the diagnosis and treatment of MPM.

In plain English

This article was a review, not a new study. The authors summarized published research on treating malignant pleural mesothelioma (MPM), which they described as mainly linked to asbestos exposure. They named no fiber types and gave no method for choosing the studies reviewed. The review covered surgery, chemotherapy, radiation, immunotherapy and molecular targets. It stated that median survival for MPM is between 9 and 17 months. It cited a clinical trial of 456 patients in which cisplatin with pemetrexed gave longer overall survival (12.1 versus 9.3 months). It described radiation results as disappointing and said no trial of anti-angiogenic drugs had shown efficacy. Citing their own earlier laboratory work on the protein EphA2, the authors reported that MPM cell lines carried high levels of EphA2 while normal mesothelial cells did not, and that silencing EphA2 reduced the cancer cells' growth. The authors concluded that EphA2 may be a potential target for future therapy. They said its mechanisms are not clearly understood and that more cell-line and animal work is needed.

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 research on treatment of malignant pleural mesothelioma and on molecular targets, especially the receptor EphA2. No search method or study-selection criteria are described.
• Who was studied: No study population of its own. The review drew on published clinical trials, animal studies and cell-line studies of malignant pleural mesothelioma. It gives no dates, number of studies or selection method.
• Exposure: This is not an exposure study. Asbestos is named as the main cause of MPM, with no fiber types, products, jobs or doses given. The review's subject is treatments (surgery, chemotherapy, radiation, immunotherapy, targeted drugs) and the EphA2 receptor.
• Main results:
  • The review stated that median survival for MPM is between 9 and 17 months despite advances in diagnosis and treatment.
  • Citing an earlier clinical trial of 456 MPM patients, the review reported that cisplatin combined with pemetrexed gave significantly longer overall survival (12.1 versus 9.3 months). The authors described this regimen as the standard first-line treatment for advanced MPM.
  • The review described the outcome of radiation therapy for MPM as disappointing.
  • The review stated that, to date, no clinical trial of anti-angiogenic agents had shown efficacy in improving response or overall survival in MPM.
  • Citing an earlier phase-II trial in a small group of MPM patients, the review reported no correlation between EGFR receptor expression and response to the drug gefitinib.
  • Citing their own earlier laboratory work, the authors reported that MPM cell lines express high levels of receptor EphA2 and that normal mesothelial cells did not express it.
  • Citing their own earlier work, the authors reported that silencing EphA2 with siRNA significantly reduced mesothelioma cell growth and induced cell death (apoptosis) in MPM cells.
  • Citing their own earlier work, the authors reported that activating EphA2 with its ligand EphrinA1 induced the microRNA let-7 in MPM cells, which they linked to suppression of the Ras oncogene.
• The authors' conclusion: The authors concluded that only modest success has been achieved in MPM therapy. They argued that research should be directed at targeting the EphA2 receptor, which they described as a potential candidate for future therapies, while saying further cell-line and animal work is needed.
• Limitations the authors state:
  • The authors noted that the treatment studies they reviewed have limitations such as small sample size, non-randomized design and patient selection bias, which could affect their outcomes.
  • The authors stated that the molecular mechanisms by which EphA2 activation inhibits tumor growth are not clearly understood.
  • The authors stated that it is still far from understood how best the Eph-Ephrin system can be targeted.
  • The authors stated that further work with cell lines and animal models is needed.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Neoplasm, Prognosis, Mesothelial Cells, Pleura, Pericardium, Median Overall Survival, Biomarker.

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