The challenge of targeted therapies for gastric cancer patients: the beginning of a long journey

Bibliography

• Jamal A, Bray F, Center MM, et al. Global Cancer statistics. CA Cancer J Clin 2011;61:69-90
   PubMed Web of Science ®Google Scholar
• Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013;49(6):1374-403
   PubMed Web of Science ®Google Scholar
• Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin 2014;64(1):9-29
   PubMed Web of Science ®Google Scholar
• Siegel R, Naishadham D, Jamal A. Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin 2012;62(5):283-98
   PubMed Web of Science ®Google Scholar
• Power DG, Kelsen DP, Shah MA. Advanced gastric cancer- -slow but steady progress. Cancer Treat Rev 2010;36(5):384-92
   PubMed Web of Science ®Google Scholar
• Wagner AD, Grothe W, Haerting J, et al. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 2006;24(18):2903-9
   PubMed Web of Science ®Google Scholar
• Price TJ, Shapiro JD, Segelov E, et al. Management of advanced gastric cancer. Expert Rev Gastroenterol Hepatol 2012;6(2):199-208
   PubMed Web of Science ®Google Scholar
• Wagner AD, Grothe W, Behl S, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2005;2):CD004064
   Google Scholar
• Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358(1):36-46
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Moiseyenko VM, Tjiulandin S, et al. Phase III study of decetaxel and cisplatin plus fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study group. J Clin Oncol 2006;24(31):4991-7
   PubMed Web of Science ®Google Scholar
• Thuss-Patience PC, Kretzschmar A, Bichev D, et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer- - a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 2011;47(15):2306-14
   PubMed Web of Science ®Google Scholar
• Kang JH, Lee SI, Lim do H, et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 2012;30(13):1513-18
   PubMed Web of Science ®Google Scholar
• Ford HE, Marshall A, Bridgewater JA, et al. Docetaxel verus active symptom control for refractory oesophagogastic adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol 2014;15(1):78-86
   PubMed Web of Science ®Google Scholar
• Milne AN, Carneiro F, O'Morain C, et al. Nature meets nurture: molecular genetics of gastric cancer. Hum Genet 2009;126(5):615-28
   PubMed Web of Science ®Google Scholar
• Nagarajan N, Bertrand D, Hillmer AM, et al. Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol 2012;13(12):R115
   PubMed Web of Science ®Google Scholar
• Dancey JE, Bedard PL, Onetto N, et al. The genetic bases for cancer decision. Cell 2012;148(3):409-20
   PubMed Web of Science ®Google Scholar
• Deng N, Goh LK, Wang H, et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 2012;61(5):673-84
   PubMed Web of Science ®Google Scholar
• Bennett C, Paterson IM, Corbishley CM, et al. Expression of growth factor and epidermal growth factor receptor encoded transcripts in human gastric tissues. Cancer Res 1989;49(8):2104-11
   PubMed Web of Science ®Google Scholar
• Sugiyama K, Yonemura Y, Miyazaki I. Immunohistochemical study of epidermal growth factor and epidermal growth factor receptor in gastric carcinoma. Cancer 1989;63(8):1557-61
   PubMed Web of Science ®Google Scholar
• Yonemura Y, Sugiyama K, Fishida S, et al. Tissue status of epidermal growth factor and its receptor as an indicator of poor prognosis in patients with gastric cancer. Anal Cell Pathol 1991;3(6):343-50
   PubMedGoogle Scholar
• Hirono Y, Tsugawa K, Fishida S, et al. Amplification of epidermal growth factor receptor gene and its relationship to survival in human gastric cancer. Oncology 1995;52(3):182-8
   PubMed Web of Science ®Google Scholar
• Kandel C, Leclair F, Bou-Hanna C, et al. Association of HER1 amplification with poor prognosis in well differentiated gastric carcinomas. J Clin Pathol 2014;67(4):307-12
   PubMed Web of Science ®Google Scholar
• Hong L, Han Y, Yang J, et al. Prognostic value of epidermal growth factor receptor in patients with gastric cancer: a meta-analysis. Gene 2013;529(1):69-72
   PubMed Web of Science ®Google Scholar
• Pinto C, Di Fabio F, Siena S, et al. Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 2007;18(3):510-17
   PubMed Web of Science ®Google Scholar
• Pinto C, Di Fabio F, Barone C, et al. Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study). BR J Cancer 2009;101(8):1261-8
   PubMed Web of Science ®Google Scholar
• Han SW, Oh DY, Im SA, et al. Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer. Br J Cancer 2009;100(2):298-304
   PubMed Web of Science ®Google Scholar
• Waddle T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol 2013;14(6):481-9
   PubMed Web of Science ®Google Scholar
• Lordick F, Kang YK, Chung HC, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 2013;14(6):490-9
   PubMed Web of Science ®Google Scholar
• Sakai K, Mori S, Kawamoto T, et al. Expression of epidermal growth factor receptors on human gastric epithelia and gastric carcinomas. J Natl Cancer Inst 1986;77(5):1047-52
   PubMed Web of Science ®Google Scholar
• Albarello L, Pecciarini L, Doglioni C. HER2 testing in gastric cancer. Adv Anat Pathol 2011;18(1):53-9
   PubMed Web of Science ®Google Scholar
• Reichelt U, Duesedau P, Tsourlakis MCh, et al. Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus. Mod Pathol 2007;20(1):120-9
   PubMed Web of Science ®Google Scholar
• Marx AH, Tharun L, Muth J, et al. HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol 2009;40(6):769-77
   PubMed Web of Science ®Google Scholar
• Bozzetti C, Negri FV, Lagrasta CA, et al. Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer 2011;104(9):1372-6
   PubMed Web of Science ®Google Scholar
• Ross JS, McKenna BJ. The HER-2/neu oncogene in tumours of the gastrointestinal tract. Cancer Invest 2001;19(5):554-68
   PubMed Web of Science ®Google Scholar
• Chan DS, Twine CP, Lewis WG. Systematic review and meta-analysis of the influence of HER2 expression and amplification in operable oesophageal cancer. J Gastrointest Surg 2012;16(10):1821-9
   PubMed Web of Science ®Google Scholar
• Fisher SB, Fisher KE, Squires MH III, et al. HER2 in resected gastric cancer: is there prognostic value? J Surg Oncol 2014;109(2):61-6
   PubMed Web of Science ®Google Scholar
• Jorgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer-A systematic analysis of data from literature. J Cancer 2012;3:137-44
   PubMed Web of Science ®Google Scholar
• Dawood S, Broglio K, Buzdar AU, et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 2009;28(1):92-8
   PubMed Web of Science ®Google Scholar
• Qiu MZ, Li Q, Wang ZQ, et al. HER2-positive patients receiving trastuzumab treatment have a comparable prognosis with HER2-negative advanced gastric cancer patients: a prospective cohort observation. Int J Cancer 2014;134(10):2468-77
   PubMed Web of Science ®Google Scholar
• Wong H, Yau T. Targeted therapy in the management of advanced gastric cancer: are we making progress in the era of personalized medicine? Oncologist 2012;17(3):346-58
   PubMed Web of Science ®Google Scholar
• Grávalos C, Gomez-Martin C, Rivera F, et al. Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer. Clin Transl Oncol 2011;13(3):179-84
   PubMed Web of Science ®Google Scholar
• Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alon for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376(9742):687-97
   PubMed Web of Science ®Google Scholar
• Gomez-Martin C, Plaza JC, Pazo-Cid R, et al. Level of HER2 gene amplification predicts response and overall serviva in HER2-positive advanced gastric cancer treated with trastuzumab. J Clin Oncol 2013;31(35):4445-52
   PubMed Web of Science ®Google Scholar
• Dose determination of Taxotere, Eloxatin and Xeloda (TEX) in combination with Herceptin in patients with HER2 positive non-resectable oesophagus, cardia or gastric cancer. (ECV) . Available from: http://clinicaltrials.gov/ct2/show/NCT01295086?term=gastric+cancer+trastuzumab&rank=33 [Accessed on 9th February 2014]
   Google Scholar
• HELOISE study: a study of Herceptin (trastuzumab) in combination with cisplatin/capecitabine chemotherapy in patients with HER2-positive metastatic gastric or gastro-esophageal junction cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT01450696?term=GASTRIC+CANCER+TRASTUZUMAB&rank=23 [Accessed on 9th February 2014]
   Google Scholar
• Kim JW, Kim HP, Im SA, et al. The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines. Cancer Lett 2008;272(2):296-306
   PubMed Web of Science ®Google Scholar
• LaBonte MJ, Manegold PC, Wilson PM, et al. The dual EGFR/HER-2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN-38. Int J Cancer 2009;125(12):2957-69
   PubMed Web of Science ®Google Scholar
• Wainberg ZA, Anghel A, Desai AJ, et al. Lapatinib, a dual EGFR and HER2 kinase inhibitor, selectively inhibits HER2-amplified human gastric cancer cells and is synergistic with trastuzumab in vitro and in vivo. Clin Cancer Res 2010;16(5):1509-19
   PubMed Web of Science ®Google Scholar
• Oshima Y, Tanaka H, Murakami H, et al. Lapatinib sensitivities of two novel trastuzumab-resistant HER2 gene-amplified gastric cancer cell lines. Gastric Cancer 2013. [ Epub ahead of print]
   Web of Science ®Google Scholar
• Iqbal S, Goldman B, Fenoglio-Preiser CM, et al. Southwest Oncology Group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer. Ann Oncol 2011;22(12):2610-15
   PubMed Web of Science ®Google Scholar
• Hecht JR, Urba SG, Koehler M, et al. Lapatinib monotherapy in recurrent upper gastrointestinal malignancy: phase II efficacy and biomarker analyses [abstract 43]. Gastrointestinal Cancers Symposium; 2008
   Google Scholar
• Galsky MD, Von Hoff D, Neubauer M, et al. Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors. J Clin Oncol 2009;27(Suppl 15s):Abstract 3541
   Google Scholar
• Hecht JR, Bang YJ, Qin S, et al. Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma (AC): the TRIO-013/LOGiC trial. J Clin Oncol 2013;31(Suppl):Abstract LBA4001
   Google Scholar
• Satoh T, Bang YJ, Wang J, et al. Interim safety analysis from TYTAN: a phase III asian study of lapatinib in combination with paclitaxel as second-line therapy in gastric cancer. J Clin Oncol 2010;28(Suppl 15):Abstract 4057
   Google Scholar
• Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367(19):1783-91
   PubMed Web of Science ®Google Scholar
• Barok M, Tanner M, Koninki K, et al. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett 2011;306(2):171-9
   PubMed Web of Science ®Google Scholar
• A randomized, multicenter, adaptive phase II/III study to evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) versus taxane (docetaxel or paclitaxel) in patients with previously treated locally advanced or metatstatic HER2-positive gastric cancer, including adenocarcinoma of the gastroesophageal junction. Available from: http://clinicaltrials.gov/ct2/show/study/NCT01641939?term=HER2+positive+gastric+cancer&rank=2&show_locs=Y#locn, [Accessed on 9th February 2014]
   Google Scholar
• Phase I study of the combination of trastuzumab emtansine (T-DM1) and capecitabine in HER2-positive metastatic breast cancer and HER2-positive locally advanced or metastatic gastric cancer patients followed by a randomized, open-label phase II study of T-DM1 and capecitabine versus T-DM1 alone in HER2-poistive metastatic breast cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT01702558?term=HER2+positive+gastric+cancer&rank=16 [Accessed on 9th February 2014]
   Google Scholar
• A phase II study of Afatinib (BIBW 2992) in patients with advanced HER2-positive trastuzumab-refractory advanced esophagogastric cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT01522768?term=HER2+gastric+cancer&rank=34 [Accessed on 9th February 2014]
   Google Scholar
• Frankiln MC, Carey KD, Vajdos FF, et al. Insights into ErbB signaling from the structure of the ErbB-pertuzumab complex. Cancer Cell 2004;5(4):317-28
   PubMed Web of Science ®Google Scholar
• Scheuer W, Friess T, Burtscher H et al. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res 2009;69(24):9330-6
   PubMed Web of Science ®Google Scholar
• Yamashite-Kashima Y, Iijima S, Yorozu K, et al. Pertuzumab in combination with trastuzumab shows significantly enhanced antitumor activity in HER2-positive human gastric cancer xenograft models. Clin Cancer Res 2011;17(15):5060-70
   PubMed Web of Science ®Google Scholar
• Baselga J, Smith BL, Rafferty EA, et al. Case records of the Massachusetts General Hospital. Case 16-2012. A 32 year woman with HER-2 positive breast cancer. N Engl J Med 2012;366(21):2018-26
   PubMedGoogle Scholar
• Swain SM, Kim SB, Cortées J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2013;14(6):461-71
   PubMed Web of Science ®Google Scholar
• A double-blind, placebo-controlled, randomized, multicenter phase III study evaluating the efficacy and safety of pertuzumab in combination with trastuzumab and chemotherapy in patients with HER2-positive metastatic gastroesophageal junction or gastric cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT01774786?term=pertuzumab+trastuzumab&rank=12 [Accessed on 9th February 2014]
   Google Scholar
• PF-00299804 Monotherapy in Patients With HER-2 Positive Advance Gastric Cancer (PF299804-AGC). Available from: http://clinicaltrials.gov/ct2/show/NCT01152853?term=NCT01152853&rank=1 [Accessed on 9th February 2014]
   Google Scholar
• Serra V, Markmann B, Scaltriti M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and Ihibits the growth of cancer cells with activating PI3K mutations. Cancer Res 2008;68(19):8022-30
   PubMed Web of Science ®Google Scholar
• Eichhorn PJ, Gili M, Scaltriti M, et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resi stance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ2365. Cancer Res 2008;68(22):9221-30
   PubMed Web of Science ®Google Scholar
• O'Regan R, Ozguroglu M, Andre F, et al. Phase III, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and vinorelbine in trastuzumab-resitant, advanced breast cancer (BOLERO-3). J Clin Oncol 2013;31(Suppl):Abstract 505
   Google Scholar
• Morrow PK, Wulf GM, Ensor J, et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol 2011;29(23):3126-32
   PubMed Web of Science ®Google Scholar
• Liang K, Esteva FJ, Albarracin C, et al. Recombinant human erythroppoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inactivation. Cancer Cell 2010;18(5):423-35
   PubMed Web of Science ®Google Scholar
• Nahta R, Yuan LX, Zhang B, et al. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res 2005;65(23):11118-28
   PubMed Web of Science ®Google Scholar
• Scaltriti M, Rojo F, Ocana A, et al. Expression of p95HER2, a truncated form of the HER2 receptor and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst 2007;99(8):628-38
   PubMed Web of Science ®Google Scholar
• Price-Schiavi SA, Jepson S, Li P, et al. Rat Muc4 (sialomucin complex) reduced binding of anti-ErbB2 antibodies ti tumor cell surfaces, a potential mechanism for herceptin resistance. Int J Cancer 2002;99(6):783-91
   PubMed Web of Science ®Google Scholar
• Castiglioni F, Tagliabue E, Campiglio M, et al. Role of exon-16-deleted HER2 in breast carcinomas. Endocr Relat Cancer 2006;13(1):221-32
   PubMed Web of Science ®Google Scholar
• Shah MA, Ramanathan RK, Ilson DH, et al. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 2006;24(33):5201-6
   PubMed Web of Science ®Google Scholar
• Shah MA, Jhawer M, Ilson DH, et al. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophagel adenocarcinoma. J Clin Oncol 2011;29(7):868-74
   PubMed Web of Science ®Google Scholar
• Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double blind, placebo-controlled phase III study. J Clin Oncol 2011;29(30):3968-76
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, de Haas S, Kang YK, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol 2012;30(17):2119-27
   PubMed Web of Science ®Google Scholar
• Scartozzi M, Pistelli M, Bittoni A, et al. Novel perspectives for the treatment of gastric cancer: from a global approach to a personalized strategy. Curr Oncol Rep 2010;12(3):175-85
   PubMedGoogle Scholar
• Hurwitz HI, Douglas PS, Middleton JP, et al. Analysis of early hypertension and clinical outcome with bevacizumab: results from seven phase III studies. Oncologist 2013;18(3):273-80
   PubMed Web of Science ®Google Scholar
• Okines AF, Reynolds AR, Cunningham D. Targeting angiogenesis in esophagogastric adenocarcinoma. Oncologist 2011;16(6):844-58
   PubMed Web of Science ®Google Scholar
• Aprile G, Bonotto M, Ongaro E, et al. Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from benchside to clinical use. Drugs 2013;73(18):2003-15
   PubMed Web of Science ®Google Scholar
• Fuchs CS, Tomasek J, Yong CJ, 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(9911):31-9
   PubMed Web of Science ®Google Scholar
• Wilke H. RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine- containing combination therapy rainbow IMCL CP12-0922 (I4T-IE- JVBE). Gastrointestinal Cancer Symposium; 2014
   Google Scholar
• O'Farrell AM, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003;101(8):3188-97
   PubMedGoogle Scholar
• Bang YJ, Kang YK, Boku N, et al. Phase II study of sunitinib as second-line treatment for advanced gastric cancer. Invest New Drugs 2011;29(6):1449-58
   PubMed Web of Science ®Google Scholar
• Moehler M, Mueller A, Hartmann JT, et al. An open-label, multicentre biomarker-oriented AIO phase II trail sunitinib for patients with chemo-refractory advanced gastric cancer. Eur J Cancer 2011;47(10):1511-20
   PubMed Web of Science ®Google Scholar
• Yi JH, Lee J, Lee J, et al. Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously trated with fluoropyrimidine and platinum. Br J Cancer 2012;106(9):1469-74
   PubMed Web of Science ®Google Scholar
• Yamada Y, Kiyota N, Fuse N, et al. A phase I study of sorafenib in combination with S-1 plus cisplatin in patients with advanced gastric cancer. Gastric Cancer 2014;17(1):161-72
   PubMed Web of Science ®Google Scholar
• Kim C, Lee JL, Choi YH, et al. Phase I dose-finding study of sorafenib in combination with capecitabine and cisplatin as first-line treatment in patients with advanced gastric cancer. Invest New Drugs 2012;30(1):306-15
   PubMed Web of Science ®Google Scholar
• Sun W, Powell M, O'Dwyer PJ, et al. Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203. J Clin Oncol 2010;28(18):2947-51
   PubMed Web of Science ®Google Scholar
• Satoh T, Yamada Y, Muro K, et al. Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients with previously untreated advanced gastric cancer. Cancer Chemother Pharmacol 2012;69(2):439-46
   PubMed Web of Science ®Google Scholar
• Eatock MM, Tebbutt NC, Bampton CL, et al. Phase II randomized, double-blind, placebo-controlled study of AMG 386 (trebananib) in combination with cisplatin and capecitabine in patients with metastatic gastro-oesophageal cancer. Ann Oncol 2013;24(3):710-18
   PubMed Web of Science ®Google Scholar
• Li J, Zhao X, Chen L, et al. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer 2010;10:529
   PubMed Web of Science ®Google Scholar
• Hung HT, Ong R, Soo KC, et al. Regorafenib, an oral multi-kinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases, potently inhibits tumor growth and angiogenesis in patient-derived xenograft models of gastric cancer. Mol Cancer Ther 2011;10(Suppl): Abstract 82
   Google Scholar
• Shah MA, Wainberg ZA, Catenacci DV, et al. Phase II study evaluating 2 doseing schedules of oral foretinib (GSK1363089), cMET/VEGFR2 inhibitor, in patients with metastatic gastric cancer. PLoS One 2013;8(3):e54014
   PubMed Web of Science ®Google Scholar
• Zhang C, Wu X, Zhang M, et al. Small molecule R1498 as a well-tolerated and orally active kinase inhibitor for hepatocellular carcinoma and gastric cancer treatment via targeting angiogenesis and mitosis pathways. PLoS One 2013;8(6):e65264
   PubMedGoogle Scholar
• Li J, Quin S, Xu J, et al. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol 2013;31(26):3219-25
   PubMed Web of Science ®Google Scholar
• Phase III Study of Apatinib Tablets in the Treatment of Advanced or Metastatic Gastric Cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT01512745?term=NCT01512745&rank=1 [Accessed on 9th February 2014]
   Google Scholar
• Kataoka Y, Mukohara T, Tomioka H, et al. Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks. Invest New Drugs 2012;30(4):1352-60
   PubMed Web of Science ®Google Scholar
• Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 2010;11(12):834-48
   PubMed Web of Science ®Google Scholar
• Gherardi E, Birchmeier W, Birchmeier C, et al. Targeting MET in cancer: rationale and progress. Nat Rev Cancer 2012;12(2):89-103
   PubMed Web of Science ®Google Scholar
• Peters S, Adjei AA. MET: a promising anticancer therapeutic target. Nat Rev Clin Oncol 2012;9(6):314-26
   PubMed Web of Science ®Google Scholar
• Ha SY, Lee J, Kang SY, et al. MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas. Mod Pathol 2013;26(12):1632-41
   PubMed Web of Science ®Google Scholar
• Graziano F, Galluccio N, Lorenzini P, et al. Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resecate gastric cancer. J Clin Oncol 2011;29(36):4789-95
   PubMed Web of Science ®Google Scholar
• Niemann HH. Structural insights into MET receptor activation. Eur J Cell Biol 2011;90(11):972-81
   PubMed Web of Science ®Google Scholar
• Oliner KS, Tang R, Anderson A, et al. Evaluation of MET pathway biomarkers in a phase II study of rilotumumab (R, AMG 102) or placebo (P) in combination with epirubicin, cisplatin, and capecitabine (ECX) in patients (pts) with locally advanced or metastatic gastric (G) or esophagogastric junction (EGJ) cancer. J Clin Oncol 2012;30(Suppl):Abstract 4005
   Google Scholar
• Merchant M, Ma X, Maun HR, et al. Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proc Natl Acad Sci USA 2013;110(32):E2987-96
   PubMed Web of Science ®Google Scholar
• Penuel E, Li C, Parab V, et al. HGF as a circulating biomarker of onartuzumab treatment in patients with advanced solid tumors. Mol Cancer Ther 2013;12(6):1122-30
   PubMed Web of Science ®Google Scholar
• Lennerz JK, Kwak EL, Ackerman A, et al. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol 2011;29(36):4803-10
   PubMed Web of Science ®Google Scholar
• Yap TA, Olmos D, Brunetto AT, et al. Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies. J Clin Oncol 2011;29(10):1271-9
   PubMed Web of Science ®Google Scholar
• Cunningham D, Bang YJ, Tabernero J, et al. MetGastric: a randomized phase III study of onartuzumab (MetMAb) in combination with m FOLFOX6 in patients with metastatic HER2-negative and MET-positive adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol 2013;31(Suppl):Abstract TPS4155
   Google Scholar
• Cunningham D, Al-BAtran AE, Davidenko I, et al. RILOMET-1: an International phase III multi center, randomized, double-blind, placebo-controlled trial of rilotumumab plus epirubicin, cisplatin, and capecitabine (ECX) as first-line therapy in patients with advanced MET-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. J Clin Oncol 2013;31(Suppl):Abstract TPS4153
   Google Scholar
• Lai AZ, Abella JV, Park M. Crosstalk in Met receptor oncogenesis. Trends Cell Biol 2009;19(10):542-51
   PubMed Web of Science ®Google Scholar
• Olwill SA, Joffroy C, Gille H, et al. A highly potent and specific MET therapeutic protein antagonist with both ligand-dependent and ligand-independent activity. Mol Cancer Ther 2013;12(11):2459-71
   PubMed Web of Science ®Google Scholar
• Meric-Bernstam F, Gonzalez-Angulo AM. Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 2009;27(13):2278-87
   PubMed Web of Science ®Google Scholar
• Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004;4(5):335-48
   PubMed Web of Science ®Google Scholar
• Martín ME, Pérez MI, Redondo C, et al. 4E binding protein 1 expression is inversely correlated to the progression of gastrointestinal cancers. Int J Biochem Cell Biol 2000;32(6):633-42
   PubMed Web of Science ®Google Scholar
• Oki E, Baba H, Tokunaga E, et al. Akt phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer. Int J Cancer 2005;117(3):376-80
   PubMed Web of Science ®Google Scholar
• Lang SA, Gaumann A, Koehl GE, 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(8):1803-10
   PubMed Web of Science ®Google Scholar
• Prins MJ, Verhage RJ, Ruurda JP, et al. Over-expression of phosphorylated mammalian target of rapamycin is associated with poor survival in oesophageal adenocarcinoma: a tissue microarray study. J Clin Pathol 2013;66(3):224-8
   PubMed Web of Science ®Google Scholar
• Wan X, Helman LJ. The biology behind mTOR inhibition in sarcoma. Oncologist 2007;12(8):1007-18
   PubMed Web of Science ®Google Scholar
• Cejka D, Preusser M, Woehrer A, et al. Everolimus (RAD001) and anti-angiogenic cyclophosphamide show long-term control of gastric cancer growth in vivo. Cancer Biol Ther 2008;7(9):1377-85
   PubMed Web of Science ®Google Scholar
• Okamoto I, Doi T, Ohtsu A, et al. Phase I clinical and pharmacokinetic study of RAD001 (everolimus) administered daily to Japanese patients with advanced solid tumors. Jpn J Clin Oncol 2010;40(1):17-23
   PubMed Web of Science ®Google Scholar
• Doi T, Muro K, Boku N, et al. Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer. J Clin Oncol 2010;28(11):1904-10
   PubMed Web of Science ®Google Scholar
• Lee SJ, Lee J, Lee J, et al. Phase II trial of capecitabine and everolimus (RAD001) combination in refractory gastric cancer patients. Invest New Drugs 2013;31(6):1580-6
   PubMed Web of Science ®Google Scholar
• Ohtsu A, Ajani JA, Bai YX, 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(31):3935-43
   PubMed Web of Science ®Google Scholar
• A Randomized, Double Blind Study Evaluating Paclitaxel With and Without RAD001 in Patients With Gastric Carcinoma After Prior Chemotherapy (AIO-STO-0111). Available from: http://clinicaltrials.gov/ct2/show/NCT01248403?term=everolimus+paclitaxel+gastric&rank=1 [Accessed on 9th February 2014]
   Google Scholar
• Foulstone E, Prince S, Zaccheo O, et al. Insulin-like growth factor ligands, receptors, and binding proteins in cancer. J Pathol 2005;205(2):145-53
   PubMed Web of Science ®Google Scholar
• Matsubara J, Yamada Y, Nakajima TE, et al. Clinical significance of insulin-like growth factor type 1 receptor and epidermal growth factor receptor in patients with advanced gastric cancer. Oncology 2008;74(1-2):76-83
   PubMed Web of Science ®Google Scholar
• King ER, Wong KK. Insulin-like growth factor: current concepts and new developments in cancer therapy. Recent Pat Anticancer Drug Discov 2012;7(1):14-30
   PubMed Web of Science ®Google Scholar
• Doi T, Fuse N, Yoshino T, et al. Phase I study of AMG 479, a fully human monoclonal antibody against the type 1 insulin-like growth factor receptor (IGF-1R), in Japanese patients (pts) with advanced solid tumors. J Clin Oncol 2011;29(Suppl 4):Abstract 318
   Google Scholar
• Molife LR, Fong PC, Paccagnella L, et al. The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study. Br J Cancer 2010;103(3):332-9
   PubMed Web of Science ®Google Scholar
• Carboni JM, Wittman M, Yang Z, et al. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol Cancer Ther 2009;8(12):3341-9
   PubMed Web of Science ®Google Scholar
• Ramalingam SS, Spigel DR, Chen D, et al. Randomized phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor-1 receptor, for advanced-stage non-small-cell lung cancer. J Clin Oncol 2011;29(34):4574-80
   PubMed Web of Science ®Google Scholar
• Robertson JF, Ferrero JM, Bourgeois H, et al. Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced, hormone-receptor-positive breast cancer: a randomised, controlled, double-blind, phase 2 trial. Lancet Oncol 2013;14(3):228-35
   PubMed Web of Science ®Google Scholar
• Bang YJ, Im SA, Lee KW, et al. Olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer: a randomized, double-blind phase II study. J Clin Oncol 2013;31(Suppl):Abstract 4013
   Google Scholar
• Efficacy and Safety Study of Olaparib in Combination With Paclitaxel to Treat Advanced Gastric Cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT01924533?term=NCT01924533&rank=1 [Accessed on 9th February 2014]
   Google Scholar
• Ueda T, Volinia S, Okumura H, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol 2010;11(2):136-46
   PubMed Web of Science ®Google Scholar
• Li X, Zhang Y, Zhang Y, et al. Survival prediction of gastric cancer by a seven-microRNA signature. Gut 2010;59(5):579-85
   PubMed Web of Science ®Google Scholar
• Yang SM, Huang C, Li XF, et al. miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN. Toxicology 2013;306:162-8
   PubMed Web of Science ®Google Scholar
• Sacconi A, Biagioni F, Canu V, et al. miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis 2012;3:e423
   PubMed Web of Science ®Google Scholar
• Nishida N, Mimori K, Fabbri M, et al. MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. Clin Cancer Res 2011;17(9):2725-33
   PubMed Web of Science ®Google Scholar
• Shen J, Stass SA, Jiang F. MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett 2013;329(2):125-36
   PubMed Web of Science ®Google Scholar
• Crowley E, Di Nicolantonio F, Loupakis F, et al. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 2013;10(8):472-84
   PubMed Web of Science ®Google Scholar