The role of mTORC1 pathway in intestinal tumorigenesis.
Activation of the mTORC1 pathway has been implicated in many types of cancer, and several mTORC1 inhibitors are currently under clinical trials for treating various cancer patients. Notably, Temsirolimus has recently been approved for treatment of advanced renal cell carcinoma. However, the role of mTORC1 pathway in colorectal tumorigenesis remains largely unknown. We have recently found that the mTORC1 pathway is activated in intestinal adenomas of Apc mutant mice, accompanied by an elevated level of mTOR protein, and that treatment with RAD001, an mTORC1 inhibitor, suppresses the growth of these polyps. Our results suggest an important role of mTORC1 pathway in colorectal cancer, as well as a therapeutic possibility for mTORC1 inhibitors in its treatment.
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Teruaki
T
Fujishita
Masahiro
M
Aoki
Makoto M
MM
Taketo
D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D000068338:Everolimus; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008954:Models, Biological; D046912:Multiprotein Complexes; D011506:Proteins; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D000068338:Everolimus; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus