1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90. PMID:
21296855
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29. PMID:
25559415
3. Power DG, Kelsen DP, Shah MA. Advanced gastric cancer--slow but steady progress. Cancer Treat Rev 2010;36:384-92. PMID:
20176443
5. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11-20. PMID:
16822992
6. Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, RieraKnorrenschild J, et al. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 2009;27:851-6. PMID:
19139439
7. Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011;29:1715-21. PMID:
21444866
8. Juergens RA, Forastiere A. Combined modality therapy of esophageal cancer. J Natl Compr Canc Netw 2008;6:851-60. PMID:
18926094
9. Haghighat P, Bekaii-Saab T. An update on biochemotherapy of advanced gastric and gastroesophageal adenocarcinoma. J Natl Compr Canc Netw 2008;6:895-900. PMID:
18926099
10. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687-97. PMID:
20728210
12. Haenszel W. Variation in incidence of and mortality from stomach cancer, with particular reference to the United States. J Natl Cancer Inst 1958;21:213-62. PMID:
13576088
13. Haenszel W, Kurihara M. Studies of Japanese migrants. I. Mortality from cancer and other diseases among Japanese in the United States. J Natl Cancer Inst 1968;40:43-68. PMID:
5635018
15. Chong ML, Loh M, Thakkar B, Pang B, Iacopetta B, Soong R. Phosphatidylinositol-3-kinase pathway aberrations in gastric and colorectal cancer: meta-analysis, co-occurrence and ethnic variation. Int J Cancer 2014;134:1232-8. PMID:
23960014
17. Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--A randomized phase III trial. J Clin Oncol 2016;34:443-51. PMID:
26628478
18. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014;383:31-9. PMID:
24094768
19. Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014;15:1224-35. PMID:
25240821
23. Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002;296:1655-7. PMID:
12040186
24. Hodgkinson CP, Sale EM, Sale GJ. Characterization of PDK2 activity against protein kinase B gamma. Biochemistry 2002;41:10351-9. PMID:
12162751
27. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006;7:606-19. PMID:
16847462
28. Duronio V. The life of a cell: apoptosis regulation by the PI3K/PKB pathway. Biochem J 2008;415:333-44. PMID:
18842113
29. Patel PH, Chadalavada RS, Chaganti RS, Motzer RJ. Targeting von Hippel-Lindau pathway in renal cell carcinoma. Clin Cancer Res 2006;12:7215-20. PMID:
17189392
30. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18:1926-45. PMID:
15314020
33. Markman B, Atzori F, Pérez-García J, Tabernero J, Baselga J. Status of PI3K inhibition and biomarker development in cancer therapeutics. Ann Oncol 2010;21:683-91. PMID:
19713247
34. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554. PMID:
15016963
35. Velho S, Oliveira C, Ferreira A, Ferreira AC, Suriano G, Schwartz S Jr, et al. The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer 2005;41:1649-54. PMID:
15994075
37. Sukawa Y, Yamamoto H, Nosho K, Ito M, Igarashi H, Naito T, et al. HER2 expression and PI3K-Akt pathway alterations in gastric cancer. Digestion 2014;89:12-7. PMID:
24458107
38. Wen YG, Wang Q, Zhou CZ, Qiu GQ, Peng ZH, Tang HM. Mutation analysis of tumor suppressor gene PTEN in patients with gastric carcinomas and its impact on PI3K/AKT pathway. Oncol Rep 2010;24:89-95. PMID:
20514448
39. Han SY, Kato H, Kato S, Suzuki T, Shibata H, Ishii S, et al. Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay. Cancer Res 2000;60:3147-51. PMID:
10866302
41. Nam SY, Lee HS, Jung GA, Choi J, Cho SJ, Kim MK, et al. Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis. APMIS 2003;111:1105-13. PMID:
14678019
42. Maroulakou IG, Oemler W, Naber SP, Tsichlis PN. Akt1 ablation inhibits, whereas Akt2 ablation accelerates, the development of mammary adenocarcinomas in mouse mammary tumor virus (MMTV)-ErbB2/neu and MMTV-polyoma middle T transgenic mice. Cancer Res 2007;67:167-77. PMID:
17210696
44. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009;9:550-62. PMID:
19629070
47. Shor B, Gibbons JJ, Abraham RT, Yu K. Targeting mTOR globally in cancer: thinking beyond rapamycin. Cell Cycle 2009;8:3831-7. PMID:
19901542
49. Ramanathan RK, McDonough SL, Kennecke HF, Iqbal S, Baranda JC, Seery TE, et al. A phase II study of MK-2206, an allosteric inhibitor of AKT as second-line therapy for advanced gastric and gastroesophageal junction (GEJ) cancer: A SWOG Cooperative Group trial (S1005). J Clin Oncol 2014;32(5(Suppl)):Abstract No. 4041.
50. Bang YJ, Kang YK, Alsina M, Wainberg ZA, Chau I, Zhu J, et al. JAGUAR: A randomized phase II study of the AKT inhibitor ipatasertib (GDC-0068) versus placebo in combination with mFOLFOX6 chemotherapy in patients (pts) with locally advanced or metastatic HER2-negative gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma. J Clin Oncol 2014;32(5(Suppl)):Abstract No. TPS4147.
52. Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res 2008;68:8022-30. PMID:
18829560
54. Belmont PJ, Jiang P, McKee TD, Xie T, Isaacson J, Baryla NE, et al. Resistance to dual blockade of the kinases PI3K and mTOR in KRAS-mutant colorectal cancer models results in combined sensitivity to inhibition of the receptor tyrosine kinase EGFR. Sci Signal 2014;7:ra107. PMID:
25389372
55. Sheppard KE, Cullinane C, Hannan KM, Wall M, Chan J, Barber F, et al. Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors. Eur J Cancer 2013;49:3936-44. PMID:
24011934
57. Cejka D, Preusser M, Woehrer A, Sieghart W, Strommer S, Werzowa J, et al. Everolimus (RAD001) and anti-angiogenic cyclophosphamide show long-term control of gastric cancer growth in vivo. Cancer Biol Ther 2008;7:1377-85. PMID:
18708754
58. Fuereder T, Jaeger-Lansky A, Hoeflmayer D, Preusser M, Strommer S, Cejka D, et al. mTOR inhibition by everolimus counteracts VEGF induction by sunitinib and improves anti-tumor activity against gastric cancer in vivo. Cancer Lett 2010;296:249-56. PMID:
20471160
59. Lee KH, Hur HS, Im SA, Lee J, Kim HP, Yoon YK, et al. RAD001 shows activity against gastric cancer cells and overcomes 5-FU resistance by downregulating thymidylate synthase. Cancer Lett 2010;299:22-8. PMID:
20727673
60. Lang SA, Gaumann A, Koehl GE, Seidel U, Bataille F, Klein D, et al. Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer 2007;120:1803-10. PMID:
17230506
61. Doi T, Muro K, Boku N, Yamada Y, Nishina T, Takiuchi H, et al. Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer. J Clin Oncol 2010;28:1904-10. PMID:
20231677
62. Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol 2013;31:3935-43. PMID:
24043745
66. Wainberg ZA, Soares HP, Patel R, DiCarlo B, Park DJ, Liem A, et al. Phase II trial of everolimus in patients with refractory metastatic adenocarcinoma of the esophagus, gastroesophageal junction and stomach: possible role for predictive biomarkers. Cancer Chemother Pharmacol 2015;76:61-7. PMID:
25969130
68. Lei Z, Tan IB, Das K, Deng N, Zouridis H, Pattison S, et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology 2013;145:554-65. PMID:
23684942
70. Janku F, Garrido-Laguna I, Wheler JJ, Hong DS, Naing A, Falchook GS, et al. Screening for PIK3CA mutations, PTEN loss, and RAS/RAF mutations in early-phase protocols with PI3K/mTOR pathway inhibitors. J Clin Oncol 2011;29(Suppl):Abstract No. 10507.
71. Britten CD. PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types. Cancer Chemother Pharmacol 2013;71:1395-409. PMID:
23443307
72. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 2005;121:179-93. PMID:
15851026
75. Tenbaum SP, Ordóñez-Morán P, Puig I, Chicote I, Arqués O, Landolfi S, et al. β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Nat Med 2012;18:892-901. PMID:
22610277
77. Bedard P, Tabernero J, Kurzrock R, Britten CD, Stathis A, Perez-Garcia JM, et al. A phase lb, open-label, multicenter, dose-escalation study of the oral pan-PI3K inhibitor BKM120 in combination with the oral MEK1/2 inhibitor GSK1120212 in patients (pts) with selected advanced solid tumors. J Clin Oncol 2012;30(Suppl):Abstract No. 3003.
78. LoRusso P, Shapiro G, Pandya SS, Kwak EL, Jones C, Belvin M, et al. A first-in-human phase Ib study to evaluate and c.w.t.p.-P. K.i.G.-. the MEK inhibitor GDC-0973, in patients with advanced solid tumors. J Clin Oncol 2012;30(Suppl):Abstract No. 2566.
79. Shimizu T, Tolcher AW, Papadopoulos KP, Beeram M, Rasco DW, Smith LS, et al. The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer. Clin Cancer Res 2012;18:2316-25. PMID:
22261800