The allosteric AKT inhibitor, MK2206, decreases tumor growth and invasion in patient derived xenografts of endometrial cancer

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7-30; PMID:26742998; https://doi.org/10.3322/caac.21332
   PubMed Web of Science ®Google Scholar
• Gallup DG, Stock RJ. Adenocarcinoma of the endometrium in women 40 years of age or younger. Obstet Gynecol 1984; 64:417-20; PMID:6462572
   PubMed Web of Science ®Google Scholar
• Voss MA, Ganesan R, Ludeman L, McCarthy K, Gornall R, Schaller G, Wei W, Sundar S. Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer-a clinical and pathological evaluation. Gynecol Oncol 2012; 124:15-20; PMID:21864888; https://doi.org/10.1016/j.ygyno.2011.07.030
   PubMed Web of Science ®Google Scholar
• Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, Weng LP, Eng C. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000; 92:924-30; PMID:10841828; https://doi.org/10.1093/jnci/92.11.924
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497:67-73; PMID:23636398; https://doi.org/10.1038/nature12113
   PubMed Web of Science ®Google Scholar
• Levine RL, Cargile CB, Blazes MS, van Rees B, Kurman RJ, Ellenson LH. PTEN mutations and microsatellite instability in complex atypical hyperplasia, a precursor lesion to uterine endometrioid carcinoma. Cancer Res 1998; 58:3254-8; PMID:9699651
   PubMed Web of Science ®Google Scholar
• Unno K, Ono M, Winder AD, Maniar KP, Paintal AS, Yu Y, Wei JJ, Lurain JR, Kim JJ. Establishment of human patient-derived endometrial cancer xenografts in NOD scid gamma mice for the study of invasion and metastasis. PLoS One 2014; 9:e116064; PMID:25542024; https://doi.org/10.1371/journal.pone.0116064
   PubMed Web of Science ®Google Scholar
• Kim JJ, Kurita T, Bulun SE. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev 2013; 34:130-62; PMID:23303565; https://doi.org/10.1210/er.2012-1043
   PubMed Web of Science ®Google Scholar
• Lee, II, Maniar K, Lydon JP, Kim JJ. Akt regulates progesterone receptor B-dependent transcription and angiogenesis in endometrial cancer cells. Oncogene 2016; 35:5191-201; PMID:26996671; https://doi.org/10.1038/onc.2016.56
   PubMed Web of Science ®Google Scholar
• Pant A, Lee, II, Lu Z, Rueda BR, Schink J, Kim JJ. Inhibition of AKT with the orally active allosteric AKT inhibitor, MK2206, sensitizes endometrial cancer cells to progestin. PLoS One 2012; 7:e41593; PMID:22911820; https://doi.org/10.1371/journal.pone.0041593
   PubMed Web of Science ®Google Scholar
• Hoekstra AV, Ward EC, Hardt JL, Lurain JR, Singh DK, Buttin BM, Schink JC, Kim JJ. Chemosensitization of endometrial cancer cells through AKT inhibition involves FOXO1. Gynecol Oncol 2008; 108:609-18; PMID:18234299; https://doi.org/10.1016/j.ygyno.2007.11.007
   PubMed Web of Science ®Google Scholar
• Neubauer NL, Ward EC, Patel P, Lu Z, Lee I, Blok LJ, Hanifi-Moghaddam P, Schink J, Kim JJ. Progesterone receptor-B induction of BIRC3 protects endometrial cancer cells from AP1-59-mediated apoptosis. Horm Cancer 2011; 2:170-81; PMID:21760855; https://doi.org/10.1007/s12672-011-0065-7
   PubMedGoogle Scholar
• Ward EC, Hoekstra AV, Blok LJ, Hanifi-Moghaddam P, Lurain JR, Singh DK, Buttin BM, Schink JC, Kim JJ. The regulation and function of the forkhead transcription factor, Forkhead box O1, is dependent on the progesterone receptor in endometrial carcinoma. Endocrinology 2008; 149:1942-50; PMID:18096667; https://doi.org/10.1210/en.2007-0756
   PubMed Web of Science ®Google Scholar
• Eaton JL, Unno K, Caraveo M, Lu Z, Kim JJ. Increased AKT or MEK1/2 activity influences progesterone receptor levels and localization in endometriosis. J Clin Endocrinol Metab 2013; 98:E1871-9; PMID: 24064688; https://doi.org/10.1210/jc.2013-1661
   PubMed Web of Science ®Google Scholar
• Kim TH, Yu Y, Luo L, Lydon JP, Jeong JW, Kim JJ. Activated AKT pathway promotes establishment of endometriosis. Endocrinology 2014; 155:1921-30; PMID:24605828; https://doi.org/10.1210/en.2013-1951
   PubMed Web of Science ®Google Scholar
• Depreeuw J, Hermans E, Schrauwen S, Annibali D, Coenegrachts L, Thomas D, Luyckx M, Gutierrez-Roelens I, Debruyne D, Konings K, et al. Characterization of patient-derived tumor xenograft models of endometrial cancer for preclinical evaluation of targeted therapies. Gynecol Oncol 2015; 139:118-26; PMID:26232337; https://doi.org/10.1016/j.ygyno.2015.07.104
   PubMed Web of Science ®Google Scholar
• Groeneweg JW, Hernandez SF, Byron VF, DiGloria CM, Lopez H, Scialabba V, Kim M, Zhang L, Borger DR, Tambouret R, et al. Dual HER2 targeting impedes growth of HER2 gene-amplified uterine serous carcinoma xenografts. Clin Cancer Res 2014; 20:6517-28; PMID:25294905; https://doi.org/10.1158/1078-0432.CCR-14-1647
   PubMed Web of Science ®Google Scholar
• Haldorsen IS, Popa M, Fonnes T, Brekke N, Kopperud R, Visser NC, Rygh CB, Pavlin T, Salvesen HB, McCormack E, et al. Multimodal Imaging of Orthotopic Mouse Model of Endometrial Carcinoma. PLoS One 2015; 10:e0135220; PMID:26252891; https://doi.org/10.1371/journal.pone.0135220
   PubMed Web of Science ®Google Scholar
• Bradford LS, Rauh-Hain A, Clark RM, Groeneweg JW, Zhang L, Borger D, Zukerberg LR, Growdon WB, Foster R, Rueda BR. Assessing the efficacy of targeting the phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway in endometrial cancer. Gynecol Oncol 2014; 133:346-52; PMID:24561032; https://doi.org/10.1016/j.ygyno.2014.02.022
   PubMed Web of Science ®Google Scholar
• Ishikawa H, Ishi K, Serna VA, Kakazu R, Bulun SE, Kurita T. Progesterone is essential for maintenance and growth of uterine leiomyoma. Endocrinology 2010; 151:2433-42; PMID:20375184; https://doi.org/10.1210/en.2009-1225
   PubMed Web of Science ®Google Scholar
• Ono M, Yin P, Navarro A, Moravek MB, Coon JSt, Druschitz SA, Serna VA, Qiang W, Brooks DC, Malpani SS, et al. Paracrine activation of WNT/beta-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Proc Natl Acad Sci U S A 2013; 110:17053-8; PMID:24082114; https://doi.org/10.1073/pnas.1313650110
   PubMed Web of Science ®Google Scholar
• Sefton EC, Qiang W, Serna V, Kurita T, Wei JJ, Chakravarti D, Kim JJ. MK2206, an AKT inhibitor, promotes caspase-independent cell death and inhibits leiomyoma growth. Endocrinology 2013; 154:4046-57; PMID:24002033; https://doi.org/10.1210/en.2013-1389
   PubMed Web of Science ®Google Scholar
• van Gurp L, Loomans CJ, van Krieken PP, Dharmadhikari G, Jansen E, Ringnalda FC, Beerling E, van Rheenen J, de Koning EJ. Sequential intravital imaging reveals in vivo dynamics of pancreatic tissue transplanted under the kidney capsule in mice. Diabetologia 2016; 59:2387-92; PMID: 27443307; https://doi.org/10.1007/s00125-016-4049-6
   PubMed Web of Science ®Google Scholar
• Ishii K, Shappell SB, Matusik RJ, Hayward SW. Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma. Lab Invest 2005; 85:1086-103; PMID:15980886; https://doi.org/10.1038/labinvest.3700310
   PubMed Web of Science ®Google Scholar
• Lee CH, Xue H, Sutcliffe M, Gout PW, Huntsman DG, Miller DM, Gilks CB, Wang YZ. Establishment of subrenal capsule xenografts of primary human ovarian tumors in SCID mice: potential models. Gynecol Oncol 2005; 96:48-55; PMID:15589579; https://doi.org/10.1016/j.ygyno.2004.09.025
   PubMed Web of Science ®Google Scholar
• Parmar H, Young P, Emerman JT, Neve RM, Dairkee S, Cunha GR. A novel method for growing human breast epithelium in vivo using mouse and human mammary fibroblasts. Endocrinology 2002; 143:4886-96; PMID:12446616; https://doi.org/10.1210/en.2002-220570
   PubMed Web of Science ®Google Scholar
• Press JZ, Kenyon JA, Xue H, Miller MA, De Luca A, Miller DM, Huntsman DG, Gilks CB, McAlpine JN, Wang YZ. Xenografts of primary human gynecological tumors grown under the renal capsule of NOD/SCID mice show genetic stability during serial transplantation and respond to cytotoxic chemotherapy. Gynecol Oncol 2008; 110:256-64; PMID:18547621; https://doi.org/10.1016/j.ygyno.2008.03.011
   PubMed Web of Science ®Google Scholar
• Yang S, Jia Y, Liu X, Winters C, Wang X, Zhang Y, Devor EJ, Hovey AM, Reyes HD, Xiao X, et al. Systematic dissection of the mechanisms underlying progesterone receptor downregulation in endometrial cancer. Oncotarget 2014; 5:9783-97; PMID:25229191; https://doi.org/10.18632/oncotarget.2392
   PubMed Web of Science ®Google Scholar
• Kashkoush S, El Moghazy W, Kawahara T, Gala-Lopez B, Toso C, Kneteman NM. Three-dimensional tumor volume and serum alpha-fetoprotein are predictors of hepatocellular carcinoma recurrence after liver transplantation: refined selection criteria. Clin Transplant 2014; 28:728-36; PMID:24708263; https://doi.org/10.1111/ctr.12373
   PubMed Web of Science ®Google Scholar