Emerging translational therapies for mesothelioma

Our plain-English summary of Emerging translational therapies for mesothelioma, by H.I. Pass, B.W. Robinson, J.R. Testa, et al (Chest, 1999).

The study

• Authors: H.I. Pass, B.W. Robinson, J.R. Testa, M. Carbone
• Journal: Chest
• Published: 1999;116(6 Suppl):455S-460S
• Type of article: Review
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma remains a therapeutic and diagnostic problem. Translational mechanisms for treatment of the disease are emerging from newly learned characteristics of the tumor on a molecular, cellular, and extracellular basis. Although slow to reach the clinical arena, these potential strategies do show proof of principle in the in vitro and in vivo settings, and some, including adenoviral molecular chemotherapy, have completed phase I testing. This review describes the rationale and status of these newer treatment ideas.

In plain English

This article was a review, not an original study. The authors described the reasoning behind, and progress of, newer molecular and immune-based treatment ideas for malignant pleural mesothelioma. These included gene therapy approaches (suicide genes, blocking tumor growth signals, boosting immune responses, replacing faulty tumor suppressor genes) and vaccination against the SV40 large T antigen. It did not study asbestos exposure. Most of the work reviewed was done in cell lines and animals. In a phase I trial at the University of Pennsylvania, 21 patients received an adenovirus carrying the herpes simplex thymidine kinase gene into the chest cavity, followed by ganciclovir. Dose-limiting toxicity was not reached, and gene transfer was documented in 11 of 20 assessable patients. In a study by Boutin and colleagues, interferon-gamma given into the chest cavity of 89 patients gave an overall response rate of 20%, and 45% in stage I disease. The authors concluded that these strategies showed proof of principle in laboratory and animal settings but were slow to reach the clinic.

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: Review of emerging molecular and immunotherapeutic treatments for malignant pleural mesothelioma
• Who was studied: No study population of its own. The review covered published and some unpublished cell-line, animal and early clinical studies of treatments for malignant pleural mesothelioma (MPM).
• Exposure: Not an asbestos exposure study. The 'exposures' reviewed were experimental treatments: gene therapy (molecular chemotherapy, autocrine/paracrine interference, genetic immunopotentiation, mutation compensation), immunotherapy with interferons and interleukin-2, and vaccination against SV40 large T antigen.
• Main results:
  • In a phase I trial at the University of Pennsylvania (cited as Sterman et al.), 21 previously untreated patients received intrapleural adenovirus-delivered herpes simplex thymidine kinase gene plus ganciclovir. Dose-limiting toxicity was not reached, and gene transfer was documented in 11 of 20 assessable patients, in a dose-related fashion.
  • In a study by Boutin et al., intrapleural interferon-gamma given to 89 patients produced 8 histologically confirmed complete and 9 partial responses. The overall response rate was 20%, and 45% for patients with stage I disease.
  • In a study by Astoul et al., intrapleural interleukin-2 given to 22 patients with MPM produced 11 partial responses and 1 complete response. Disease was stable in 3 patients and progressed in 7. Overall median survival was 18 months, and 24- and 36-month survival rates for responders were 58% and 41%.
  • In a Southwest Oncology Group study of intramuscular interferon-beta, there were no complete or partial responses.
  • In a study by Robinson et al., a vaccinia interleukin-2 construct was injected into tumors in six patients, and no tumor regression occurred.
• The authors' conclusion: The authors concluded that these newer strategies, although slow to reach the clinic, showed proof of principle in laboratory (in vitro) and animal (in vivo) settings, and that many potential molecular and immunotherapeutic targets were under investigation.

Topics

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

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

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• Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach — D. Lisini, S. Lettieri, et al. (2021)
• Emerging therapies in malignant pleural mesothelioma — M. Cinausero, K. Rihawi, et al. (2019)
• Emerging biological therapies for the treatment of malignant pleural mesothelioma — A.P. Davis, S.C. Kao, et al. (2021)
• A novel translational approach for human malignant pleural mesothelioma: heparanase-assisted dual virotherapy — Y. Watanabe, T. Kojima, et al. (2010)
• Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies — A. Bononi, A. Napolitano, et al. (2015)

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