The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors
Open accessAbstract
Non-small-cell lung cancer is the leading cause of cancer-related death worldwide. Chemotherapies such as the topoisomerase II (TopoII) inhibitor etoposide effectively reduce disease in a minority of patients with this cancer; therefore, alternative drug targets, including epigenetic enzymes, are under consideration for therapeutic intervention. A promising potential epigenetic target is the methyltransferase EZH2, which in the context of the polycomb repressive complex 2 (PRC2) is well known to tri-methylate histone H3 at lysine 27 (H3K27me3) and elicit gene silencing. Here we demonstrate that EZH2 inhibition has differential effects on the TopoII inhibitor response of non-small-cell lung cancers in vitro and in vivo. EGFR and BRG1 mutations are genetic biomarkers that predict enhanced sensitivity to TopoII inhibitor in response to EZH2 inhibition. BRG1 loss-of-function mutant tumours respond to EZH2 inhibition with increased S phase, anaphase bridging, apoptosis and TopoII inhibitor sensitivity. Conversely, EGFR and BRG1 wild-type tumours upregulate BRG1 in response to EZH2 inhibition and ultimately become more resistant to TopoII inhibitor. EGFR gain-of-function mutant tumours are also sensitive to dual EZH2 inhibition and TopoII inhibitor, because of genetic antagonism between EGFR and BRG1. These findings suggest an opportunity for precision medicine in the genetically complex disease of non-small-cell lung cancer.
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Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950
Chou, T.-C., & Talalay, P. (1984) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(84)90007-4 · Cited by 7,178
Drug combination studies and their synergy quantification using the Chou-Talalay method
Chou, T.-C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-1947 · Cited by 5,739
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V. J., Richardson, A. L., & Weinberg, R. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.034 · Cited by 3,759
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection.
Li, C., & Wong, W. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.31 · Cited by 3,133
A decade of exploring the cancer epigenome—biological and translational implications
Baylin, S. B., & Jones, P. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3130 · Cited by 2,871
More powerful procedures for multiple significance testing
Hochberg, Y., & Benjamini, Y. (1990) · Statistics in Medicine · doi:10.1002/sim.4780090710 · Cited by 2,715
Gene-expression profiles predict survival of patients with lung adenocarcinoma
Beer, D. G., Kardia, S. L. R., Huang, C.-C., Giordano, T. J., Levin, A. M., Misek, D. E., Lin, L., Chen, G., Gharib, T. G., Thomas, D. G., et al. (2002) · Nature Medicine · doi:10.1038/nm733 · Cited by 2,025
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Kim, K. H., & Roberts, C. W. M. (2016) · Nature Medicine · doi:10.1038/nm.4036 · Cited by 1,471
Cancer Stem Cells: Basic Concepts and Therapeutic Implications
Nassar, D., & Blanpain, C. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044438 · Cited by 869
Combining epigenetic drugs with other therapies for solid tumours — past lessons and future promise
Morel, D., Jeffery, D., Aspeslagh, S., Almouzni, G., & Postel-Vinay, S. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0267-4 · Cited by 445
Maintaining cell identity: PRC2-mediated regulation of transcription and cancer
Comet, I., Riising, E. M., Leblanc, B., & Helin, K. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.83 · Cited by 432
The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer
Hodges, C., Kirkland, J. G., & Crabtree, G. R. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026930 · Cited by 414
Metadata
- Authors
- Fillmore, C. M., Xu, C., Desai, P. T., Berry, J. M., Rowbotham, S. P., Lin, Y.-J., Zhang, H., Marquez, V. E., Hammerman, P. S., Wong, K.-K., & Kim, C. F.
- Venue
- Nature
- Published
- 2015-01-28
- Volume
- 520
- Issue
- 7546
- Pages
- 239-242
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2013149980
- Cited by
- 255
- References
- 12
- FWCI
- 15.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Fillmore, C. M., Xu, C., Desai, P. T., Berry, J. M., Rowbotham, S. P., Lin, Y.-J., Zhang, H., Marquez, V. E., Hammerman, P. S., Wong, K.-K., & Kim, C. F. (2015). EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors. Nature. https://doi.org/10.1038/nature14122
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