Germline and Somatic Mutations in Human Mesothelioma and Lessons from Asbestos-Exposed Genetically Engineered Mouse Models

Cheung, Mitchell; Menges, Craig W.; Testa, Joseph R.

doi:10.1007/978-3-319-53560-9_8

Cited by 3 publications

(3 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these proteins we observed an increased abundance of multiple proteins of biological interest in the asbestos group. The heterogeneous effects observed in the asbestos group is not uncommon due to several reasons, (1) it is an insoluble (fibrous) agent and is not available to all cells (or all surfaces of tissues) uniformly and (2) it is well known that only a small percentage of asbestos‐exposed individuals develop mesothelioma suggesting a susceptibility issue …”

Section: Discussionmentioning

confidence: 99%

“…The heterogeneous effects observed in the asbestos group is not uncommon due to several reasons, (1) it is an insoluble (fibrous) agent and is not available to all cells (or all surfaces of tissues) uniformly and (2) it is well known that only a small percentage of asbestos-exposed individuals develop mesothelioma suggesting a susceptibility issue. 17,18 Moreover, as this study was intended to yield insight on potential exosomal protein biomarkers for asbestos exposure we believe the proteins with most increased abundance for asbestos exposed animals are of most interest. Within this subset of identified exosomal proteins there are some potential implications in the biology of asbestos exposure.…”

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

Mouse serum exosomal proteomic signature in response to asbestos exposure

Munson

Lam

MacPherson

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Asbestos-induced diseases like fibrosis and mesothelioma are very aggressive, without any treatment options. These diseases are diagnosed only at the terminal stages due to lack of early stage biomarkers. The recent discovery of exosomes as circulating biomarkers led us to look for exosomal biomarkers of asbestos exposure in mouse blood. In our model, mice were exposed to asbestos as a single bolus dose by oropharyngeal aspiration. Fifty-six days later blood was collected, exosomes were isolated from plasma and characterized and subjected to proteomic analysis using Tandem Mass Tag labeling. We identified many proteins, some of which were more abundant in asbestos exposed mouse serum exosomes, and three selected proteins were validated by immunoblotting. Our study is the first to show that serum exosomal proteomic signatures can reveal some important proteins relevant to asbestos exposure that have the potential to be validated as candidate biomarkers. We hope to extrapolate the positive findings of this study to humans in future studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Mouse serum exosomal proteomic signature in response to asbestos exposure

Munson

Lam

MacPherson

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…Numerous investigators have induced MM in rats and mice via injection or inhalation of asbestos fibers (34) or in hamsters through exposure to SV40 (35). Notably, several studies have shown that the MMs induced in rats via asbestos inhalation do not exhibit cytogenetic or gene expression patterns similar to those seen in their human tumor counterparts nor do they show inactivation of genes implicated as drivers in human MM (36)(37)(38)(39).…”

Section: Rodents As Models Of Asbestos Carcinogenicity and Mesotheliomentioning

confidence: 99%

Preclinical Models of Malignant Mesothelioma

Testa

Berns

2020

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

show abstract

A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models

Hillen,

Candi,

Vanderhoydonck

et al. 2023

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

The Hippo pathway and its downstream effectors, the YAP and TAZ transcriptional co-activators, are deregulated in multiple different types of human cancer and are required for cancer cell phenotypes in vitro and in vivo, while largely dispensable for tissue homeostasis in adult mice. YAP/TAZ and their main partner transcription factors, the TEAD1-4 factors, are therefore promising anti-cancer targets. Due to frequent YAP/TAZ hyperactivation caused by mutations in the Hippo pathway components NF2 and LATS2, mesothelioma is one of the prime cancer types predicted to be responsive to YAP/TAZ-TEAD inhibitor treatment. Mesothelioma is a devastating disease for which currently no effective treatment options exist. Here, we describe a novel covalent YAP/TAZ-TEAD inhibitor, SWTX-143, that binds to the palmitoylation pocket of all four TEAD isoforms. SWTX-143 caused irreversible and specific inhibition of the transcriptional activity of YAP/TAZ-TEAD in Hippo-mutant tumor cell lines. More importantly, YAP/TAZ-TEAD inhibitor treatment caused strong mesothelioma regression in subcutaneous xenograft models with human cells and in an orthotopic mesothelioma mouse model. Finally, SWTX-143 also selectively impaired the growth of NF2-mutant kidney cancer cell lines, suggesting that the sensitivity of mesothelioma models to these YAP/TAZ-TEAD inhibitors can be extended to other tumor types with aberrations in Hippo signaling. In brief, we describe a novel and specific YAP/TAZ-TEAD inhibitor that has potential to treat multiple Hippo-mutant solid tumor types.

show abstract

Germline and Somatic Mutations in Human Mesothelioma and Lessons from Asbestos-Exposed Genetically Engineered Mouse Models

Cited by 3 publications

References 90 publications

Mouse serum exosomal proteomic signature in response to asbestos exposure

Mouse serum exosomal proteomic signature in response to asbestos exposure

Preclinical Models of Malignant Mesothelioma

A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models

Contact Info

Product

Resources

About