Switching off malignant mesothelioma: exploiting the hypoxic microenvironment

Our plain-English summary of Switching off malignant mesothelioma: exploiting the hypoxic microenvironment, by N. Nabavi, K.L. Bennewith, A. Churg, et al (Genes & Cancer, 2016).

The study

• Authors: N. Nabavi, K.L. Bennewith, A. Churg, Y. Wang, C.C. Collins, L. Mutti
• Journal: Genes & Cancer
• Published: 2016;7(11-12):340-354
• Type of article: Review
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesotheliomas are aggressive, asbestos-related cancers with poor patient prognosis, typically arising in the mesothelial surfaces of tissues in pleural and peritoneal cavity. The relative unspecific symptoms of mesotheliomas, misdiagnoses, and lack of precise targeted therapies call for a more critical assessment of this disease. In the present review, we categorize commonly identified genomic aberrations of mesotheliomas into their canonical pathways and discuss targeting these pathways in the context of tumor hypoxia, a hallmark of cancer known to render solid tumors more resistant to radiation and most chemo-therapy. We then explore the concept that the intrinsic hypoxic microenvironment of mesotheliomas can be Achilles' heel for targeted, multimodal therapeutic intervention.

In plain English

This article is a review and reported no new patient data or experiments. The authors grouped gene changes common in malignant mesothelioma, mainly pleural mesothelioma, into biological pathways. They discussed these in relation to tumor hypoxia (low-oxygen areas in tumors), which they described as making solid tumors more resistant to radiation and most chemotherapy. Citing other studies, the review stated that mesotheliomas are particularly hypoxic and that more than 90% are positive for the hypoxia marker CA-IX. It also stated that BAP1 is deleted or mutated in about 60% of mesotheliomas, and that in pleural mesotheliomas NF2 is altered in about 45% and LATS1/2 in about 30%. The review described drugs designed to be activated under low oxygen and listed clinical trials in pleural mesothelioma. The authors noted that links between hypoxia and several of these pathways remain unestablished or insufficiently studied in mesothelioma. They suggested the low-oxygen environment of mesotheliomas could serve as an 'Achilles' heel' for targeted drug delivery. They asked whether therapies would work better if tumor hypoxia were carefully assessed and treatment combined with hypoxia-based therapies.

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 (no new data)
• Who was studied: No study population; the review covered published literature on malignant mesothelioma, focusing mainly on pleural mesothelioma
• Exposure: Not an exposure study. The review's subject was tumor hypoxia and gene changes. In its background it stated, citing other work, that mesothelioma is often caused by asbestos exposure and can also be caused by other mineral fibers such as erionite and by inherited BAP1 mutations.
• Main results:
  • Citing other studies, the review stated that mesotheliomas are particularly hypoxic (low-oxygen) tumors, based on hypoxia markers and PET-CT imaging
  • Citing other studies, the review stated that more than 90% of mesotheliomas are positive for CA-IX, a marker of hypoxia
  • Citing other studies, the review stated that BAP1 is the tumor suppressor gene most commonly deleted or mutated in mesotheliomas, in about 60% of cases
  • Citing other studies, the review stated that in pleural mesotheliomas NF2 is altered in about 45% and LATS1/2 in about 30%
  • The review described drugs designed to be activated under low-oxygen conditions as a treatment strategy
  • The authors noted that the link between hypoxia and NF2/LATS2 has not been studied in mesothelioma
  • The authors noted that a direct link between PI3K/AKT/MTOR and hypoxia has not been established in mesothelioma
  • The authors noted that the link between hypoxia and proteolysis has not been thoroughly investigated in mesothelioma
• The authors' conclusion: The authors suggested that the hypoxic environment of mesotheliomas could be used as an 'Achilles' heel' for targeted drug delivery. They asked whether new therapies would be more effective if tumor hypoxia were carefully assessed and the therapies were given in combination with hypoxia-based therapies.

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Prognosis, Peritoneal Cavity, Mesothelioma, Hypoxia.

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