title: Simultaneous targeting of EGFR and mTOR inhibits the growth of colorectal             carcinoma cells.
abstract: Epidermal growth factor receptor (EGFR) is highly expressed in colorectal             carcinomas and, as a result, it leads to the activation of downstream mammalian             target of rapamycin (mTOR) kinase pathways for cancer growth and progression.             Clinical and preclinical studies, however, have shown that inhibition of epidermal             growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) alone is             not sufficient to treat colorectal carcinomas. In search of effective combination             therapies, we show here that simultaneous targeting of EGFR with its inhibitor,             erlotinib and mTOR with its inhibitor, rapamycin inhibits the phosphorylation             and activation of downstream phosphatidylinositol 3-kinase (PI3K), Akt, mTOR and             extracellular-signal-regulated kinase 1/2 (Erk1/2) pathways, resulting in the             inhibition of cell cycle progression and the growth of both KRAS wild-type and             mutated colorectal carcinoma cells. This study has demonstrated the principle             that the combination of erlotinib and rapamycin may provide an effective therapy             for colorectal carcinomas.
authors.affiliation: Department of Colorectal Surgery, The Third Hospital of Jilin University, Changchun, Jilin 130033, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Shuohui
authors.initials: S
authors.lastname: Gao
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Anita C
authors.initials: AC
authors.lastname: Bellail
authors.forename: Chunhai
authors.initials: C
authors.lastname: Hao
authors.forename: Tongjun
authors.initials: T
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D018631:ras Proteins; C117307:KRAS protein, human; C546842:MTOR protein, human