Gene therapy for mesothelioma and lung cancer

Our plain-English summary of Gene therapy for mesothelioma and lung cancer, by A. Vachani, E. Moon, E. Wakeam, et al (American Journal of Respiratory Cell and Molecular Biology, 2010).

The study

• Authors: A. Vachani, E. Moon, E. Wakeam, S.M. Albelda
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 2010;42(4):385-93
• Type of article: Review
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Both malignant pleural mesothelioma and advanced stage lung cancer are associated with a poor prognosis. Unfortunately, current treatment regimens have had only a modest effect on their progressive course. Gene therapy for thoracic malignancies represents a novel therapeutic approach and has been evaluated in a number of clinical trials over the last two decades. Using viral vectors or anti-sense RNA, strategies have included induction of apoptosis, tumor suppressor gene replacement, suicide gene expression, cytokine-based therapy, various vaccination approaches, and adoptive transfer of modified immune cells. This review will consider the clinical results, limitations, and future directions of gene therapy trials for thoracic malignancies.

In plain English

This article was a review, not a new study. The authors described clinical trials of gene therapy carried out over about two decades in patients with malignant pleural mesothelioma and lung cancer. They covered the delivery methods used and strategies such as suicide genes, cytokine genes, tumor suppressor gene replacement, antisense therapy and vaccines. In one series of mesothelioma trials they described, an adenovirus carrying a suicide gene reached the tumor in 23 of 30 patients, and two patients survived for long periods (one 7 years, one still alive after 10 years). In a trial of adenovirus carrying interferon-beta in 10 patients (seven with mesothelioma, three with other cancers in the pleura), four had what the authors called meaningful clinical responses. A phase II lung cancer trial of p53 gene therapy found no difference in response rates compared with lesions treated with chemotherapy alone. The authors concluded that gene therapy for lung cancer and mesothelioma had not yet reached clinical practice. The review did not address asbestos exposure.

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 clinical gene therapy trials
• Who was studied: Published and ongoing clinical trials over about two decades in patients with malignant pleural mesothelioma (MPM), malignant pleural effusions and lung cancer, including trials by the authors' own group at the University of Pennsylvania
• Exposure: No asbestos exposure was studied. The treatments reviewed were gene therapy approaches using viral vectors or antisense RNA: induction of apoptosis, tumor suppressor gene replacement, suicide genes, cytokine therapy, vaccines and modified immune cells
• Main results:
  • In the adenovirus suicide gene (Ad.HSVtk/GCV) trials in advanced MPM by Sterman and colleagues, gene transfer was shown in 23 of 30 patients
  • In those same trials, two patients at higher doses survived for long periods
  • In a Phase 1 adenovirus interferon-beta trial in 7 MPM patients and 3 patients with metastatic pleural malignancies, four patients had meaningful clinical responses (disease stability or partial regression on imaging 2 months after treatment)
  • A second interferon-beta trial with two doses was conducted in 17 patients (10 with MPM, 7 with malignant pleural effusions); antibodies against the adenovirus blocked effective gene transfer of the second dose
  • In lung cancer, a phase II study found no difference in response rates between lesions treated with Ad.p53 plus chemotherapy and lesions treated with chemotherapy alone
• The authors' conclusion: The authors concluded that the trials have generally shown safety but only intermittent efficacy, that gene therapy for lung cancer and MPM has not yet reached clinical practice, and that in their view progress is being made

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: Mesothelioma, Lung Cancer, Pleural Mesothelioma, Prognosis, Clinical Trial, Apoptosis, Tumor Suppressor Gene, Cytokine.

Related studies

• Mesothelioma: an inviting but challenging target for gene therapy — R.G. Crystal (2010)
• Gene therapy for mesothelioma — A. Vachani, E. Moon, et al. (2011)
• Gene therapy for lung neoplasms — A. Vachani, E. Moon, et al. (2011)
• Gene therapy approaches for inherited and acquired lung diseases — D.T. Curiel, J.M. Pilewski, et al. (1996)
• Gene therapy for malignant pleural mesothelioma: present and future — Y. Tada, Y. Takiguchi, et al. (2008)
• Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms — Z.G. Fridlender, J. Sun, et al. (2010)

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