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Combined targeting of AKT and mTOR using MK-2206 and RAD001 is synergistic in the treatment of cholangiocarcinoma.

Ewald F, Grabinski N, Grottke A, Windhorst S, Nörz D, Carstensen L, Staufer K, Hofmann BT, Diehl F, David K, Schumacher U, Nashan B, Jücker M.

Int J Cancer. 2013 Nov;133(9):2065-76. doi: 10.1002/ijc.28214. Epub 2013 May 29.


Combined targeting of AKT and mTOR synergistically inhibits proliferation of hepatocellular carcinoma cells.

Grabinski N, Ewald F, Hofmann BT, Staufer K, Schumacher U, Nashan B, Jücker M.

Mol Cancer. 2012 Nov 20;11:85. doi: 10.1186/1476-4598-11-85.


Increased activation of PI3K/AKT signaling pathway is associated with cholangiocarcinoma metastasis and PI3K/mTOR inhibition presents a possible therapeutic strategy.

Yothaisong S, Dokduang H, Techasen A, Namwat N, Yongvanit P, Bhudhisawasdi V, Puapairoj A, Riggins GJ, Loilome W.

Tumour Biol. 2013 Dec;34(6):3637-48. doi: 10.1007/s13277-013-0945-2. Epub 2013 Jul 6.


Antitumor activity of the combination of an HSP90 inhibitor and a PI3K/mTOR dual inhibitor against cholangiocarcinoma.

Chen MH, Chiang KC, Cheng CT, Huang SC, Chen YY, Chen TW, Yeh TS, Jan YY, Wang HM, Weng JJ, Chang PM, Liu CY, Li CP, Chao Y, Chen MH, Huang CY, Yeh CN.

Oncotarget. 2014 May 15;5(9):2372-89.


Rapamycin inhibits both motility through down-regulation of p-STAT3 (S727) by disrupting the mTORC2 assembly and peritoneal dissemination in sarcomatoid cholangiocarcinoma.

Hong SM, Park CW, Cha HJ, Kwon JH, Yun YS, Lee NG, Kim DG, Nam HG, Choi KY.

Clin Exp Metastasis. 2013 Feb;30(2):177-87. doi: 10.1007/s10585-012-9526-9. Epub 2012 Aug 9.


Combined targeting of mTOR and AKT is an effective strategy for basal-like breast cancer in patient-derived xenograft models.

Xu S, Li S, Guo Z, Luo J, Ellis MJ, Ma CX.

Mol Cancer Ther. 2013 Aug;12(8):1665-75. doi: 10.1158/1535-7163.MCT-13-0159. Epub 2013 May 20.


Akt inhibitors MK-2206 and nelfinavir overcome mTOR inhibitor resistance in diffuse large B-cell lymphoma.

Petrich AM, Leshchenko V, Kuo PY, Xia B, Thirukonda VK, Ulahannan N, Gordon S, Fazzari MJ, Ye BH, Sparano JA, Parekh S.

Clin Cancer Res. 2012 May 1;18(9):2534-44. doi: 10.1158/1078-0432.CCR-11-1407. Epub 2012 Feb 14.


Vertical blockade of the IGFR- PI3K/Akt/mTOR pathway for the treatment of hepatocellular carcinoma: the role of survivin.

Ou DL, Lee BS, Lin LI, Liou JY, Liao SC, Hsu C, Cheng AL.

Mol Cancer. 2014 Jan 3;13:2. doi: 10.1186/1476-4598-13-2.


The combination of RAD001 and MK-2206 exerts synergistic cytotoxic effects against PTEN mutant gastric cancer cells: involvement of MAPK-dependent autophagic, but not apoptotic cell death pathway.

Ji D, Zhang Z, Cheng L, Chang J, Wang S, Zheng B, Zheng R, Sun Z, Wang C, Zhang Z, Liu R, Zhang X, Liu X, Wang X, Li J.

PLoS One. 2014 Jan 9;9(1):e85116. doi: 10.1371/journal.pone.0085116. eCollection 2014.


Survey of activated kinase proteins reveals potential targets for cholangiocarcinoma treatment.

Dokduang H, Juntana S, Techasen A, Namwat N, Yongvanit P, Khuntikeo N, Riggins GJ, Loilome W.

Tumour Biol. 2013 Dec;34(6):3519-28. doi: 10.1007/s13277-013-0930-9. Epub 2013 Jun 29.


The mTOR inhibitor RAD001 sensitizes tumor cells to the cytotoxic effect of carboplatin in breast cancer in vitro.

Liu H, Zang C, Schefe JH, Schwarzlose-Schwarck S, Regierer AC, Elstner E, Schulz CO, Scholz C, Possinger K, Eucker J.

Anticancer Res. 2011 Sep;31(9):2713-22.


Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells.

Martinelli E, Troiani T, D'Aiuto E, Morgillo F, Vitagliano D, Capasso A, Costantino S, Ciuffreda LP, Merolla F, Vecchione L, De Vriendt V, Tejpar S, Nappi A, Sforza V, Martini G, Berrino L, De Palma R, Ciardiello F.

Int J Cancer. 2013 Nov;133(9):2089-101. doi: 10.1002/ijc.28236. Epub 2013 May 29.


Dual targeting of the Akt/mTOR signaling pathway inhibits castration-resistant prostate cancer in a genetically engineered mouse model.

Floc'h N, Kinkade CW, Kobayashi T, Aytes A, Lefebvre C, Mitrofanova A, Cardiff RD, Califano A, Shen MM, Abate-Shen C.

Cancer Res. 2012 Sep 1;72(17):4483-93. doi: 10.1158/0008-5472.CAN-12-0283. Epub 2012 Jul 19.


Levels of p27 sensitize to dual PI3K/mTOR inhibition.

Lee M, Theodoropoulou M, Graw J, Roncaroli F, Zatelli MC, Pellegata NS.

Mol Cancer Ther. 2011 Aug;10(8):1450-9. doi: 10.1158/1535-7163.MCT-11-0188. Epub 2011 Jun 6.


Targeting the PI3K/Akt/mTOR signaling pathway in B-precursor acute lymphoblastic leukemia and its therapeutic potential.

Neri LM, Cani A, Martelli AM, Simioni C, Junghanss C, Tabellini G, Ricci F, Tazzari PL, Pagliaro P, McCubrey JA, Capitani S.

Leukemia. 2014 Apr;28(4):739-48. doi: 10.1038/leu.2013.226. Epub 2013 Jul 29.


Luteolin arrests cell cycling, induces apoptosis and inhibits the JAK/STAT3 pathway in human cholangiocarcinoma cells.

Aneknan P, Kukongviriyapan V, Prawan A, Kongpetch S, Sripa B, Senggunprai L.

Asian Pac J Cancer Prev. 2014;15(12):5071-6.


Limitations in small intestinal neuroendocrine tumor therapy by mTor kinase inhibition reflect growth factor-mediated PI3K feedback loop activation via ERK1/2 and AKT.

Svejda B, Kidd M, Kazberouk A, Lawrence B, Pfragner R, Modlin IM.

Cancer. 2011 Sep 15;117(18):4141-54. doi: 10.1002/cncr.26011. Epub 2011 Mar 8.


Perturbation of proteasome function by bortezomib leading to ER stress-induced apoptotic cell death in cholangiocarcinoma.

Vaeteewoottacharn K, Kariya R, Matsuda K, Taura M, Wongkham C, Wongkham S, Okada S.

J Cancer Res Clin Oncol. 2013 Sep;139(9):1551-62. doi: 10.1007/s00432-013-1473-6. Epub 2013 Jul 23.


Anti-myeloma activity of Akt inhibition is linked to the activation status of PI3K/Akt and MEK/ERK pathway.

Ramakrishnan V, Kimlinger T, Haug J, Painuly U, Wellik L, Halling T, Rajkumar SV, Kumar S.

PLoS One. 2012;7(11):e50005. doi: 10.1371/journal.pone.0050005. Epub 2012 Nov 21.


Preclinical evaluation of combined TKI-258 and RAD001 in hepatocellular carcinoma.

Chan SL, Wong CH, Lau CP, Zhou Q, Hui CW, Lui VW, Ma BB, Chan AT, Yeo W.

Cancer Chemother Pharmacol. 2013 Jun;71(6):1417-25. doi: 10.1007/s00280-013-2139-4. Epub 2013 Apr 2.

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