The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors
Open accessAbstract
Mutations or aberrant upregulation of EZH2 occur frequently in human cancers, yet clinical benefits of EZH2 inhibitor (EZH2i) remain unsatisfactory and limited to certain hematological malignancies. We profile global posttranslational histone modification changes across a large panel of cancer cell lines with various sensitivities to EZH2i. We report here oncogenic transcriptional reprogramming mediated by MLL1's interaction with the p300/CBP complex, which directs H3K27me loss to reciprocal H3K27ac gain and restricts EZH2i response. Concurrent inhibition of H3K27me and H3K27ac results in transcriptional repression and MAPK pathway dependency in cancer subsets. In preclinical models encompassing a broad spectrum of EZH2-aberrant solid tumors, a combination of EZH2 and BRD4 inhibitors, or a triple-combination including MAPK inhibition display robust efficacy with very tolerable toxicity. Our results suggest an attractive precision treatment strategy for EZH2-aberrant tumors on the basis of tumor-intrinsic MLL1 expression and concurrent inhibition of epigenetic crosstalk and feedback MAPK activation.
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Cites
The polycomb group protein EZH2 is involved in progression of prostate cancer
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., et al. (2002) · Nature · doi:10.1038/nature01075 · Cited by 2,717
Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma
Ally, A., Balasundaram, M., Carlsen, R., Chuah, E., Clarke, A., Dhalla, N., Holt, R. A., Jones, S. J. M., Lee, D., Ma, Y., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.046 · Cited by 2,490
Self-citationEZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations
McCabe, M. T., Ott, H. M., Ganji, G., Korenchuk, S., Thompson, C., Van Aller, G. S., Liu, Y., Graves, A. P., III, A. D. P., Diaz, E., et al. (2012) · Nature · doi:10.1038/nature11606 · Cited by 1,786
Proteogenomics connects somatic mutations to signalling in breast cancer
CPTAC, N., Mertins, P., Mani, D. R., Ruggles, K. V., Gillette, M. A., Clauser, K. R., Wang, P., Wang, X., Qiao, J. W., Cao, S., et al. (2016) · Nature · doi:10.1038/nature18003 · Cited by 1,676
Morin, R. D., Johnson, N. A., Severson, T. M., Mungall, A. J., An, J., Goya, R., Paul, J. E., Boyle, M., Woolcock, B. W., Kuchenbauer, F., et al. (2010) · Nature Genetics · doi:10.1038/ng.518 · Cited by 1,521
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Patient-derived tumour xenografts as models for oncology drug development
Tentler, J. J., Tan, A. C., Weekes, C. D., Jimeno, A., Leong, S., Pitts, T. M., Arcaroli, J. J., Messersmith, W. A., & Eckhardt, S. G. (2012) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2012.61 · Cited by 1,277
Targeting bromodomains: epigenetic readers of lysine acetylation
Filippakopoulos, P., & Knapp, S. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4286 · Cited by 1,243
EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.
Bracken, A. P., Pasini, D., Capra, M., Prosperini, E., Colli, E., & Helin, K. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg542 · Cited by 1,196
Extraction, purification and analysis of histones
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Cited by
EZH2: a novel target for cancer treatment
Duan, R., Du, W., & Guo, W. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00937-8 · Cited by 926
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
Histone Lysine Methylation Dynamics Control EGFR DNA Copy-Number Amplification
Clarke, T. L., Tang, R., Chakraborty, D., Van Rechem, C., Ji, F., Mishra, S., Ma, A., Kaniskan, H. Ü., Jin, J., Lawrence, M. S., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0463 · Cited by 50
Metadata
- Authors
- Huang, X., Yan, J., Zhang, M., Wang, Y., Chen, Y., Fu, X., Wei, R., Zheng, X.-L., Liu, Z., Zhang, X., Yang, H., Hao, B., Shen, Y.-Y., Su, Y., Cong, X., Huang, M., Tan, M., Ding, J., & Geng, M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 175
- Issue
- 1
- Pages
- 186-199.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2892042921
- Cited by
- 264
- References
- 49
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Huang, X., Yan, J., Zhang, M., Wang, Y., Chen, Y., Fu, X., Wei, R., Zheng, X.-L., Liu, Z., Zhang, X., Yang, H., Hao, B., Shen, Y.-Y., Su, Y., Cong, X., Huang, M., Tan, M., Ding, J., & Geng, M. (2018). Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors. Cell. https://doi.org/10.1016/j.cell.2018.08.058
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