The hippo pathway provides novel insights into lung cancer and mesothelioma treatment

Our plain-English summary of The hippo pathway provides novel insights into lung cancer and mesothelioma treatment, by X.L. Liu, R. Zuo, W.B. Ou (Journal of Cancer Research and Clinical Oncology, 2018).

The study

• Authors: X.L. Liu, R. Zuo, W.B. Ou
• Journal: Journal of Cancer Research and Clinical Oncology
• Published: 2018;144(11):2097-2106
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: Lung cancer and mesothelioma are two types of respiratory disease that have fatal courses and poor prognoses. Although a substantial number of targeted small molecules and antibody drugs have been developed, the 5-year survival rates of these patients remain relatively low. Moreover, most patients inevitably develop clinical resistance to treatment. Therefore, novel therapeutic options and cancer prognostic biomarkers are urgently needed.

Methods: In this review, we summarized the recent literature from various electronic databases, including PubMed, and highlighted the most advanced findings regarding the hippo pathway in lung cancer and mesothelioma.

Conclusion: The hippo signaling transduction pathway has been demonstrated to play crucial roles in lung cancer and mesothelioma pathogenesis, including tumor development and multidrug resistance, and is emerging as a promising therapeutic target, potentially providing new tools for the detection of these tumors at an early stage.

In plain English

This article is a narrative review, not a new study. The authors summarized published research, found through databases including PubMed, on the hippo pathway, a chain of signaling proteins inside cells, in lung cancer and malignant mesothelioma. They did not say how many studies they included or how they chose them. Asbestos appears only in the background, where the authors note that mesothelioma is thought to typically be caused by asbestos fiber exposure. The review reported findings from other researchers, including strong activation of the protein YAP in over 70% of mesothelioma tumors, LATS2 gene deletions or mutations in 10 of 45 mesotheliomas, and abnormal NF2 (merlin) expression in 50% of mesothelioma cases. For non-small cell lung cancer, a cited study of 181 patients linked TAZ overexpression to shorter overall survival (25.1 versus 44.3 months). Cited laboratory studies linked YAP and TAZ to resistance to lung cancer drugs. The authors concluded that the pathway is emerging as a promising treatment target and may help detect these tumors early. They noted that many mechanisms remain unclear.

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 literature. The article reports no new data, and it does not describe its search dates or how studies were selected.
• Who was studied: Published laboratory, animal and clinical studies on the hippo pathway in lung cancer (mainly non-small cell lung cancer) and malignant mesothelioma. The number of studies reviewed is not stated.
• Exposure: This is not a study of asbestos exposure. It reviews a cell signaling pathway. Asbestos is mentioned only in background text, which cites other work saying malignant mesothelioma is thought to typically be caused by asbestos fiber exposure. No fiber types, products, jobs or doses are studied.
• Main results:
  • The review cites other studies reporting strong YAP activation in over 70% of malignant mesothelioma tumors from patients, and LATS2 mutations in about 10 to 20% of malignant mesotheliomas.
  • The review cites a study (Murakami et al. 2011) that found LATS2 deletions or mutations in 10 of 45 malignant mesotheliomas.
  • The review cites other work reporting abnormal expression of Merlin/NF2, an upstream regulator of the hippo pathway, in 50% of malignant mesothelioma cases.
  • The review cites a laboratory study (Tanaka et al. 2017) in which specific inhibitors of the enzyme HMG-CoA reductase increased YAP phosphorylation and reduced the proliferation and migration of mesothelioma cells.
  • The review cites a study (Xie et al. 2012) comparing 181 non-small cell lung cancer patients with 20 normal lung tissues. In that study, TAZ overexpression was correlated with shorter overall survival (25.1 versus 44.3 months).
  • The review cites a study (Luo et al. 2014) in lung cancer patients that linked high LATS2 expression to longer disease-free survival (p = 0.002) and longer overall survival (p = 0.041) than low LATS2 expression.
  • Based on cited cell studies, the authors suggest that YAP and/or TAZ may contribute to resistance to EGFR-targeted drugs in non-small cell lung cancer.
• The authors' conclusion: The authors concluded that the hippo pathway plays roles in the development of lung cancer and mesothelioma and in their drug resistance. They wrote that it is emerging as a promising therapeutic target and could potentially provide tools to detect these tumors at an early stage.
• Limitations the authors state:
  • The authors state that the detailed mechanisms by which YAP, TAZ and other pathways drive drug resistance in non-small cell lung cancer remain unknown.
  • The authors state that a proposed feedback loop between CD44 and YAP in mesothelioma is their own hypothesis and has not yet been verified.

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: Lung Cancer, Mesothelioma, Biomarker.

Related studies

• Hippo pathway gene mutations in malignant mesothelioma: revealed by RNA and targeted exon sequencing — A. Miyanaga, M. Masuda, et al. (2015)
• The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications — S.L. Teoh, S. Das (2017)
• TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation — A. Matsushita, T. Sato, et al. (2019)
• Inactivation of Merlin in malignant mesothelioma cells and the Hippo signaling cascade dysregulation — Y. Sekido (2011)
• Aberrant expression of NPPB through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations — T. Sato, K. Akao, et al. (2023)
• Immunohistochemistry for NF2, LATS1/2, and YAP/TAZ Fails to Separate Benign From Malignant Mesothelial Proliferations — B.S. Sheffield, J. Lorette, et al. (2016)

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