The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk Analyses in Patient-Derived Xenografts
Open accessAbstract
Preclinical models based on patient-derived xenografts have remarkable specificity in distinguishing transformed human tumor cells from non-transformed murine stromal cells computationally. We obtained 29 pancreatic ductal adenocarcinoma (PDAC) xenografts from either resectable or non-resectable patients (surgery and endoscopic ultrasound-guided fine-needle aspirate, respectively). Extensive multiomic profiling revealed two subtypes with distinct clinical outcomes. These subtypes uncovered specific alterations in DNA methylation and transcription as well as in signaling pathways involved in tumor-stromal cross-talk. The analysis of these pathways indicates therapeutic opportunities for targeting both compartments and their interactions. In particular, we show that inhibiting NPC1L1 with Ezetimibe, a clinically available drug, might be an efficient approach for treating pancreatic cancers. These findings uncover the complex and diverse interplay between PDAC tumors and the stroma and demonstrate the pivotal role of xenografts for drug discovery and relevance to PDAC.
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Cites
Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621 · cited 16×
“…cancer ICGC (International Cancer Genome Consortium) project defined four subtypes of PDAC based on the transcriptomic analysis of 96 selected primary tumors (Bailey et al., 2016), which they named squamous, pancreatic progenitor, immunogenic, and aberrantly differentiated endocrine exocrine (ADEX).”
BackgroundMethodResultInfluentialMoffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G. H., Hoadley, K. A., Rashid, N. U., Williams, L. A., Eaton, S. C., Chung, A. H., et al. (2015) · Nature Genetics · doi:10.1038/ng.3398 · Cited by 2,194
Integrated genomic characterization of pancreatic ductal adenocarcinoma
Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.007 · Cited by 2,019
Gao, H., Korn, J. M., Ferretti, S., Monahan, J. E., Wang, Y., Singh, M., Zhang, C., Schnell, C., Yang, G., Zhang, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3954 · Cited by 1,393
Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets
Witkiewicz, A. K., McMillan, E. A., Balaji, U., Baek, G., Lin, W.-C., Mansour, J., Mollaee, M., Wagner, K.-U., Koduru, P., Yopp, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms7744 · Cited by 1,115 · cited 1×
“While preliminary genomic analysis suggested that genetic alteration could define therapeutic options (Witkiewicz et al., 2015), more recent studies found no associations between any genetic alterations and therapeutic responses on a large number of drugs (Knudsen et al.”
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Pancreatic cancer stroma: an update on therapeutic targeting strategies
Hosein, A. N., Brekken, R. A., & Maitra, A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0300-1 · Cited by 950
Stratification of pancreatic ductal adenocarcinomas based on tumor and microenvironment features
Puleo, F., Nicolle, R., Blum, Y., Cros, J., Marisa, L., Demetter, P., Quertinmont, E., Svrcek, M., Elarouci, N., Iovanna, J., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.033 · Cited by 563
Self-citationAccurate and efficient detection of gene fusions from RNA sequencing data
Uhrig, S., Ellermann, J., Walther, T., Burkhardt, P., Fröhlich, M., Hutter, B., Toprak, U. H., Neumann, O., Stenzinger, A., Scholl, C., et al. (2021) · Genome Research · doi:10.1101/gr.257246.119 · Cited by 526
Stromal biology and therapy in pancreatic cancer: ready for clinical translation?
Neesse, A., Bauer, C. A., Öhlund, D., Lauth, M., Buchholz, M., Michl, P., Tuveson, D. A., & Gress, T. M. (2019) · Gut · doi:10.1136/gutjnl-2018-316451 · Cited by 353
Microenvironmental Determinants of Pancreatic Cancer
Hessmann, E., Buchholz, S. M., Demir, I. E., Singh, S. K., Gress, T. M., Ellenrieder, V., & Neesse, A. (2020) · Physiological Reviews · doi:10.1152/physrev.00042.2019 · Cited by 331
Metadata
- Authors
- Nicolle, R., Blum, Y., Marisa, L., Loncle, C., Gayet, O., Moutardier, V., Turrini, O., Giovannini, M., Bian, B., Bigonnet, M., Rubis, M., Elarouci, N., Armenoult, L., Ayadi, M., Duconseil, P., Gasmi, M., Ouaissi, M., Maignan, A., Lomberk, G., Boher, J.-M., Ewald, J., Bories, E., Garnier, J., Goncalves, A., Poizat, F., Raoul, J.-L., Secq, V., Garcia, S., Grandval, P., Barraud-Blanc, M., Norguet, E., Gilabert, M., Delpero, J.-R., Roques, J., Calvo, E., Guillaumond, F., Vasseur, S., Urrutia, R., de Reyniès, A., Dusetti, N., & Iovanna, J.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 21
- Issue
- 9
- Pages
- 2458-2470
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2769127580
- Cited by
- 199
- References
- 5
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- gold
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