mTORC2 signaling drives the development and progression of pancreatic cancer

Driscoll, David R. and Karim, Saadia A. and Sano, Makoto and Gay, David M. and Jacob, Wright and Yu, Jun and Mizukami, Yusuke and Gopinathan, Aarthi and Jodrell, Duncan I. and Evans, T. R. Jeffry and Bardeesy, Nabeel and Hall, Michael N. and Quattrochi, Brian J. and Klimstra, David S. and Barry, Simon T. and Sansom, Owen J. and Lewis, Brian C. and Morton, Jennifer P.. (2016) mTORC2 signaling drives the development and progression of pancreatic cancer. Cancer Research, 76 (23). pp. 6911-6923.

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Official URL: http://edoc.unibas.ch/44701/

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mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for Cancer Research
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2017 13:39
Deposited On:25 Oct 2017 13:15

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