Details

Autor(en) / Beteiligte

• Driscoll, David R
• Karim, Saadia A
• Sano, Makoto
• Gay, David M
• Jacob, Wright
• Yu, Jun
• Mizukami, Yusuke
• Gopinathan, Aarthi
• Jodrell, Duncan I
• Evans, T R Jeffry
• Bardeesy, Nabeel
• Hall, Michael N
• Quattrochi, Brian J
• Klimstra, David S
• Barry, Simon T
• Sansom, Owen J
• Lewis, Brian C
• Morton, Jennifer P

Titel

mTORC2 Signaling Drives the Development and Progression of Pancreatic Cancer

Ist Teil von

• Cancer research (Chicago, Ill.), 2016-12, Vol.76 (23), p.6911-6923

Ort / Verlag

United States

Erscheinungsjahr

2016

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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. Cancer Res; 76(23); 6911-23. ©2016 AACR.