The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and shows resistance to any therapeutic strategy used. Here we tested small-molecule inhibitors targeting chromatin regulators as possible therapeutic agents in PDAC. We show that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses PDAC development in mice by inhibiting both MYC activity and inflammatory signals. The histone deacetylase (HDAC) inhibitor SAHA synergizes with JQ1 to augment cell death and more potently suppress advanced PDAC. Finally, using a CRISPR-Cas9–based method for gene editing directly in the mouse adult pancreas, we show that de-repression of p57 (also known as KIP2 or CDKN1C) upon combined BET and HDAC inhibition is required for the induction of combination therapy–induced cell death in PDAC. SAHA is approved for human use, and molecules similar to JQ1 are being tested in clinical trials. Thus, these studies identify a promising epigenetic-based therapeutic strategy that may be rapidly implemented in fatal human tumors.
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Genome engineering using the CRISPR-Cas9 system
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A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
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Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine
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Selective inhibition of BET bromodomains
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Self-citationSelective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
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Self-citationA decade of exploring the cancer epigenome—biological and translational implications
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Whole genomes redefine the mutational landscape of pancreatic cancer
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Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis
Romero, R., Sayin, V. I., Davidson, S. M., Bauer, M. R., Singh, S. X., LeBoeuf, S. E., Karakousi, T. R., Ellis, D. C., Bhutkar, A., Sánchez-Rivera, F. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4407 · Cited by 652
Self-citationGenetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527
Orth, M., Metzger, P., Gerum, S., Mayerle, J., Schneider, G., Belka, C., Schnurr, M., & Lauber, K. (2019) · Radiation Oncology · doi:10.1186/s13014-019-1345-6 · Cited by 490
Self-citationTherapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas
Piunti, A., Hashizume, R., Morgan, M. A., Bartom, E. T., Horbinski, C. M., Marshall, S. A., Rendleman, E. J., Ma, Q., Takahashi, Y.-H., Woodfin, A. R., et al. (2017) · Nature Medicine · doi:10.1038/nm.4296 · Cited by 445
BET Proteins as Targets for Anticancer Treatment
Stathis, A., & Bertoni, F. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0605 · Cited by 463
Metadata
- Authors
- Mazur, P. K., Herner, A., Mello, S. S., Wirth, M., Hausmann, S., Sánchez-Rivera, F. J., Lofgren, S. M., Kuschma, T., Hahn, S. A., Vangala, D., Trajkovic-Arsic, M., Gupta, A., Heid, I., Noël, P. B., Braren, R., Erkan, M., Kleeff, J., Sipos, B., Sayles, L. C., Heikenwalder, M., Heßmann, E., Ellenrieder, V., Esposito, I., Jacks, T., Bradner, J. E., Khatri, P., Sweet-Cordero, E. A., Attardi, L. D., Schmid, R. M., Schneider, G., Sage, J., & Siveke, J. T.
- Venue
- Nature Medicine
- Published
- 2015-09-21
- Volume
- 21
- Issue
- 10
- Pages
- 1163-1171
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1939365747
- Cited by
- 397
- References
- 24
- FWCI
- 17.88
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Mazur, P. K., Herner, A., Mello, S. S., Wirth, M., Hausmann, S., Sánchez-Rivera, F. J., Lofgren, S. M., Kuschma, T., Hahn, S. A., Vangala, D., Trajkovic-Arsic, M., Gupta, A., Heid, I., Noël, P. B., Braren, R., Erkan, M., Kleeff, J., Sipos, B., Sayles, L. C., . . . Siveke, J. T. (2015). Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Nature Medicine. https://doi.org/10.1038/nm.3952
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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