Biomarkers and novel agents in esophago-gastric cancer: are we making progress?

References

• GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Available from: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx [Last accessed 21 May 2015]
   Google Scholar
• Surveillance, Epidemiology, and End Results Program (SEER): Cancer facts sheets: Stomach and Esophagus 2015. Available from: http://seer.cancer.gov/statfacts/html/esoph.html [Last accessed 21 May 2015]
   Google Scholar
• Edgren G, Adami H, Weiderpass E, Nyrén O. A global assessment of the oesophageal adenocarcinoma epidemic. Gut 2013;62(10):1406-14
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and 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
• 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
• Cromwell D, Palser T, van der Meulen J, et al. National oesophago-gastric cancer audit 2010. an audit of the care received by patients with oesophago-gastric cancer in England and Wales: Third Annual Report. 2010
   Google Scholar
• Thallinger CM, Raderer M, Hejna M. Esophageal cancer: a critical evaluation of systemic second-line therapy. J Clin Oncol 2011;29(35):4709-14
   PubMed Web of Science ®Google Scholar
• Ford HR, Marshall A, Bridgewater JA, et al.Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. The Lancet Oncology 2013;15(1):78-86
   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
• Hironaka S, Ueda S, Yasui H, et al. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol 2013;31(35):4438-44
   PubMed Web of Science ®Google Scholar
• Bang YJ, Van Cutsem E, Feyereislova 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(9742):687-97
   PubMed Web of Science ®Google Scholar
• Neuzillet C, Tijeras-Raballand A, de Mestier L, et al. MEK in cancer and cancer therapy. Pharmacol Ther 2014;141(2):160-71
   PubMed Web of Science ®Google Scholar
• McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007;1773(8):1263-84
   PubMed Web of Science ®Google Scholar
• Jorissen RN, Walker F, Pouliot N, et al. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 2003;284(1):31-53
   PubMed Web of Science ®Google Scholar
• Normanno N, De Luca A, Bianco C, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006;366(1):2-16
   PubMed Web of Science ®Google Scholar
• Ushiro H, Cohen S. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J Biol Chem 1980;255(18):8363-5
   PubMed Web of Science ®Google Scholar
• Schreiber AB, Libermann TA, Lax I, et al. Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies. J Biol Chem 1983;258(2):846-53
   PubMed Web of Science ®Google Scholar
• Lonardo F, Di Marco E, King CR, et al. The normal erbB-2 product is an atypical receptor-like tyrosine kinase with constitutive activity in the absence of ligand. New Biol 1990;2(11):992-1003
   PubMedGoogle Scholar
• Guy PM, Platko JV, Cantley LC, et al. Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc Natl Acad Sci USA 1994;91(17):8132-6
   PubMed Web of Science ®Google Scholar
• Burgess AW, Cho HS, Eigenbrot C, et al. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol Cell 2003;12(3):541-52
   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
• Lordick F, Luber B, Lorenzen S, et al. Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Br J Cancer 2010;102(3):500-5
   PubMed Web of Science ®Google Scholar
• Lorenzen S, Schuster T, et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol 2009;20(10):1667-73
   PubMed Web of Science ®Google Scholar
• Enzinger PC, Burtness B, Hollis D, et al. CALGB 80403/ECOG 1206: A randomized phase II study of three standard chemotherapy regimens (ECF, IC, FOLFOX) plus cetuximab in metastatic esophageal and GE junction cancer. ASCO Meeting Abstracts 2010;28(15_suppl):4006
   Google Scholar
• Moehler M, Mueller A, et al. Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study. Ann Oncol 2011;22(6):1358-66
   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
• Waddell 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
• Gold PJ, Goldman B, Iqbal S, et al. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol 2010;5(9):1472-6
   PubMed Web of Science ®Google Scholar
• Chan JA, Blaszkowsky LS, Enzinger PC, et al. A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma. Ann Oncol 2011;22(6):1367-73
   PubMed Web of Science ®Google Scholar
• Tebbutt NC, Parry MM, Zannino D, et al. Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophagogastric cancer: the AGITG ATTAX2 trial. Br J Cancer 2013;108(4):771-4
   PubMed Web of Science ®Google Scholar
• Marshall J. Clinical implications of the mechanism of epidermal growth factor receptor inhibitors. Cancer 2006;107(6):1207-18
   PubMed Web of Science ®Google Scholar
• Bianco R, Gelardi T, Damiano V, et al. Rational bases for the development of EGFR inhibitors for cancer treatment. Int J Biochem Cell Biol 2007;39(7-8):1416-31
   PubMed Web of Science ®Google Scholar
• Doi T, Koizumi S, Siena S, et al. Efficacy, tolerability and pharmacokinetics of Gefitinib (ZD1839) in pretreated patients with metastatic gastric cancer. Proc Am Soc Clin Oncol 2003;22:258
   Google Scholar
• Ferry DR, Anderson M, Beddows K, et al.II trial of gefitinib (ZD1839) in advanced adenocarcinoma of the oesophagus incorporating biopsy before and after gefitinib. ASCO Meeting Abstracts 2004;22(14_suppl):4021
   Google Scholar
• Van Groeningen C, Richel D, Giaccone G. Gefitinib phase II study in second-line treatment of advanced esophageal cancer. J Clin Oncol 2004;22(Suppl 14S):4022
   PubMed Web of Science ®Google Scholar
• Adelstein DJ, Rybicki LA, Carroll MA, et al. Phase II trial of gefitinib for recurrent or metastatic esophageal or gastroesophageal junction (GEJ) cancer. ASCO Meeting Abstracts 2005;23(16_suppl):4054
   Google Scholar
• Janmaat ML, Gallegos-Ruiz MI, et al. Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol 2006;24(10):1612-19
   PubMed Web of Science ®Google Scholar
• Dragovich T, McCoy S, Fenoglio-Preiser CM, et al. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol 2006;24(30):4922-7
   PubMed Web of Science ®Google Scholar
• Rojo F, Tabernero J, Albanell J, et al. Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma. J Clin Oncol 2006;24(26):4309-16
   PubMed Web of Science ®Google Scholar
• Ferry DR, Anderson M, Beddard K, et al. A phase II study of gefitinib monotherapy in advanced esophageal adenocarcinoma: evidence of gene expression, cellular, and clinical response. Clin Cancer Res 2007;13(19):5869-75
   PubMed Web of Science ®Google Scholar
• Ilson DH, Kelsen D, Shah M, et al. A phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus. Cancer 2011;117(7):1409-14
   PubMed Web of Science ®Google Scholar
• Dutton SJ, Ferry DR, Blazeby JM, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial. Lancet Oncol 2014;15(8):894-904
   PubMed Web of Science ®Google Scholar
• Johnson JR, Cohen M, Sridhara R, et al. Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non–small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res 2005;11(18):6414-21
   PubMed Web of Science ®Google Scholar
• Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non–small-cell lung cancer. N Engl J Med 2005;353(2):123-32
   PubMed Web of Science ®Google Scholar
• Ciuleanu T, Stelmakh L, Cicenas S, et al. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol 2012;13(3):300-8
   PubMed Web of Science ®Google Scholar
• Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010;11(6):521-9
   PubMed Web of Science ®Google Scholar
• Wainberg ZA, Lin LS, DiCarlo B, et al. Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction. Br J Cancer 2011;105(6):760-5
   PubMed Web of Science ®Google Scholar
• Cohen MH, Williams GA, Sridhara R, et al. United States Food and Drug Administration Drug Approval summary: Gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 2004;10(4):1212-18
   PubMed Web of Science ®Google Scholar
• Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361(10):947-57
   PubMed Web of Science ®Google Scholar
• Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011;29(21):2866-74
   PubMed Web of Science ®Google Scholar
• Hara F, Aoe M, Doihara H, et al. Antitumor effect of gefitinib (’Iressa’) on esophageal squamous cell carcinoma cell lines in vitro and in vivo. Cancer Lett 2005;226(1):37-47
   PubMed Web of Science ®Google Scholar
• Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, ’Iressa’), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett 2005;579(19):4069-75
   PubMed Web of Science ®Google Scholar
• Sudo T, Mimori K, Nagahara H, et al. Identification of EGFR mutations in esophageal cancer. Eur J Surg Oncol 2007;33(1):44-8
   PubMed Web of Science ®Google Scholar
• Guo M, Liu S, Lu F. Gefitinib-sensitizing mutations in esophageal carcinoma. N Engl J Med 2006;354(20):2193-4
   PubMed Web of Science ®Google Scholar
• Drenckhan A, Grob T, Dupree A, et al. Esophageal carcinoma cell line with high EGFR polysomy is responsive to gefitinib. Langen Arch Surg 2014;399(7):879-88
   PubMed 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, Bang Y, 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
   Google Scholar
• Satoh T, Xu RH, Chung HC, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN- a randomized, Phase III study. J Clin Oncol 2014;32(19):2039-49
   PubMed Web of Science ®Google Scholar
• Yoon HH, Shi Q, Sukov WR, et al. Adverse prognostic impact of intratumor heterogeneous HER2 gene amplification in patients with esophageal adenocarcinoma. J Clin Oncol 2012;30(32):3932-8
   PubMed Web of Science ®Google Scholar
• Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res 2014;16:R22
   Google Scholar
• A study of trastuzumab emtansine versus taxane in patients with advanced gastric cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01641939
   Google Scholar
• A study of perjeta (Pertuzumab) in combination With Herceptin (Trastuzumab) and chemotherapy in patients with HER2-positive metastatic gastroesophageal junction or gastric cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01774786?term=Pertuzumab+AND+trastuzumab+AND+gastric&rank=1
   Google Scholar
• Cook KM, Figg WD. Angiogenesis inhibitors: current strategies and future prospects. CA Cancer J Clin 2010;60(4):222-43
   PubMed Web of Science ®Google Scholar
• Ballas MS, Chachoua A. Rationale for targeting VEGF, FGF, and PDGF for the treatment of NSCLC. Onco Targets Ther 2011;4:43-58
   PubMed Web of Science ®Google Scholar
• Gerber H, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-Kinase/Akt signal transduction pathway requirement FOR Flk-1/KDR activation. J Biol Chem 1998;273(46):30336-43
   PubMed Web of Science ®Google Scholar
• Shih CH, Ozawa S, Ando N, et al. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res 2000;6(3):1161-8
   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
• 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
• Shen L, Li J, Xu J, et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer 2015;18(1):168-76
   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, Van Cutsem E, Oh SC, et al. 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). ASCO Meeting Abstracts 2014;32(3_suppl):LBA7
   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
• Idelevich E, Kashtan H, Klein Y, et al. Prospective phase II study of neoadjuvant therapy with cisplatin, 5-fluorouracil, and bevacizumab for locally advanced resectable esophageal cancer. Onkologie 2012;35(7-8):427-31
   PubMed Web of Science ®Google Scholar
• Li J, Qin 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
• 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
• Wilhelm SM, Adnane L, Newell P, et al. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 2008;7(10):3129-40
   PubMed Web of Science ®Google Scholar
• Martin-Richard M, Gallego R, Pericay C, et al. Multicenter phase II study of oxaliplatin and sorafenib in advanced gastric adenocarcinoma after failure of cisplatin and fluoropyrimidine treatment. A gemcad study. Invest New Drugs 2013;31(6):1573-9
   PubMed Web of Science ®Google Scholar
• Bang Y, Kang Y, Kang WK, 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 trial of sunitinib for patients with chemo-refractory advanced gastric cancer. Eur J Cancer 2011;47(10):1511-20
   PubMed Web of Science ®Google Scholar
• Yi J, Lee J, Lee J, et al. Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum. Br J Cancer 2012;106(9):1469-74
   PubMed Web of Science ®Google Scholar
• Pavlakis KM, Tsobanis E, Martin A, et al. INTEGRATE: a randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer—a study by the Australasian Gastrointestinal Trials Group (AGITG), first results. Clin Oncol 2015;33:3
   Google Scholar
• Manning BD. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol 2004;167(3):399-403
   PubMed Web of Science ®Google Scholar
• Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006;7(8):606-19
   PubMed Web of Science ®Google Scholar
• Ljungberg B, Cowan NC, Hanbury DC, et al. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010;58(3):398-406
   PubMed Web of Science ®Google Scholar
• Chan J, Kulke M. Targeting the mTOR signaling pathway in neuroendocrine tumors. Curr Treat Opt Oncol 2014;15(3):365-79
   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
• 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
• 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
• Gavine PR, Mooney L, Kilgour E, et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res 2012;72(8):2045-56
   PubMed Web of Science ®Google Scholar
• Goetz R, Mohammadi M. Exploring mechanisms of FGF signalling through the lens of structural biology. Nat Rev Mol Cell Biol 2013;14(3):166-80
   PubMed Web of Science ®Google Scholar
• Kato H, Arao T, Matsumoto K, et al. Gene amplification of EGFR, HER2, FGFR2 and MET in esophageal squamous cell carcinoma. Int J Oncol 2013;42(4):1151-8
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Arao T, Hamaguchi T, et al. FGFR2 gene amplification and clinicopathological features in gastric cancer. Br J Cancer 2012;106(4):727-32
   PubMed Web of Science ®Google Scholar
• Su X, Zhan P, Gavine P, et al. FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study. Br J Cancer 2014;110(4):967-75
   PubMed Web of Science ®Google Scholar
• Arkenau H, Saggese M, Hollebecque A, et al. A phase 1 expansion cohort of the fibroblast growth factor receptor (FGFR) inhibitor AZD4547 in patients (pts) with advanced gastric (GC) and gastroesophageal (GOJ) cancer. J Clin Oncol 2014;32(Suppl 5s):abstract 2620
   Google Scholar
• A trial of AZD4547 with cisplatin and capecitabine for advanced cancer (FACING). Available from: www.cancerresearchuk.org/about-cancer/trials/a-trial-of-azd4547-with-cisplatin-and-capecitabine-for-advanced-cancer
   Google Scholar
• Efficacy and safety of AZD4547 versus paclitaxel in advanced gastric or gastro-oesophageal junction cancer patients (SHINE) 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT01457846?term=FGFR2+gastric&rank=1
   Google Scholar
• Bang Y, Van Cutsem E, Mansoor W, et al. A randomized, open-label phase II study of AZD4547 (AZD) versus Paclitaxel (P) in previously treated patients with advanced gastric cancer (AGC) with Fibroblast Growth Factor Receptor 2 (FGFR2) polysomy or gene amplification (amp): SHINE study. J Clin Oncol 2015;33(Suppl):abstract 4014
   Google Scholar
• Sierra JR, Tsao M. c-MET as a potential therapeutic target and biomarker in cancer. Therap Adv Med Oncol 2011;3(1 suppl):S21-35
   PubMedGoogle 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
• Lee J, Seo JW, Jun HJ, et al. Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target. Oncol Rep 2011;25(6):1517-24
   PubMed Web of Science ®Google Scholar
• Kang Y, Muro K, Ryu M, et al. A phase II trial of a selective c-Met inhibitor tivantinib (ARQ 197) monotherapy as a second-or third-line therapy in the patients with metastatic gastric cancer. Invest New Drugs 2014;32(2):355-61
   PubMed Web of Science ®Google Scholar
• Shah MA, Wainberg ZA, Catenacci DV, et al. Phase II study evaluating 2 dosing 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
• Iveson T, Donehower RC, Davidenko I, et al. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol 2014;15(9):1007-18
   PubMed Web of Science ®Google Scholar
• Cunningham D, Tebbutt N, Davidenko I, et al. Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study. J Clin Oncol 2015;33(Suppl):abstract 4000
   Google Scholar
• Shah M, Bang Y, Lordick F, et al. METGastric: A phase III study of onartuzumab plus mFOLFOX6 in patients with metastatic HER2-negative (HER2-) and MET-positive (MET+) adenocarcinoma of the stomach or gastroesophageal junction (GEC). J Clin Oncol 2015;33(Suppl):abstract 4012
   Google Scholar
• Zhang X, Lin M, van Golen KL, et al. Multiple signaling pathways are activated during insulin-like growth factor-I (IGF-I) stimulated breast cancer cell migration. Breast Cancer Res Treat 2005;93(2):159-68
   PubMed Web of Science ®Google Scholar
• Rowinsky EK, Youssoufian H, Tonra JR, et al. IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor. Clin Cancer Res 2007;13(18 Pt 2):5549s-55s
   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
• Molife L, Fong P, 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
• Paclitaxel with or without cixutumumab as second-line therapy in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT01142388?term=cixutumumab+AND+esophageal&rank=1
   Google Scholar
• Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol 2007;19(7):813-24
   PubMed Web of Science ®Google Scholar
• Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med 2015;372(26):2521-32
   PubMed Web of Science ®Google Scholar
• Muro K, Bang Y, Shankaran V, et al. Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab in KEYNOTE-012. J Clin Oncol 2015;33(Suppl 3):abstract 3
   Google Scholar
• Doi T, Piha-Paul S, Ibrahim Jalal S, et al. Pembrolizumab (MK-3475) for patients (pts) with advanced esophageal carcinoma: Preliminary results from Keynote-028. J Clin Oncol 2015;33(Suppl):abstract 4010
   Google Scholar
• A study of pembrolizumab (MK-3475) in participants with recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma (MK-3475-059/KEYNOTE-059). Available from: https://clinicaltrials.gov/ct2/show/NCT02335411?term=pembrolizumab+gastric&rank=2
   Google Scholar
• Herceg Z, Wang Z. Functions of poly (ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res 2001;477(1):97-110
   PubMed Web of Science ®Google Scholar
• Olaparib. Available from: www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm427598.htm
   Google Scholar
• Kubota E, Williamson CT, Ye R, et al. Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines. Cell Cycle 2014;13(13):2129-37
   PubMed Web of Science ®Google Scholar
• Bang Y, Im S, Lee K, et al. Olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer: a randomized, double-blind phase II study. J Clin Oncol 2013
   PubMed Web of Science ®Google Scholar
• Efficacy and safety study of olaparib in combination with paclitaxel to treat advanced gastric cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01924533?term=olaparib+gastric&rank=2
   Google Scholar
• Catalogue of Somatic Mutations in Cancer Database. Available from: http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/
   Google Scholar
• Petty R, Dahle-Smith A, Miedzybrodzka Z, et al. Epidermal growth factor receptor copy number gain (EGFR CNG) and response to gefitinib in esophageal cancer (EC): Results of a biomarker analysis of a phase III trial of gefitinib versus placebo (TRANS-COG). J Clin Oncol 2014;32:5s
   Google Scholar
• FOCUS 4: Molecular selection of therapy in metastatic colorectal cancer: a molecularly stratified randomised control trial programme. Available from: www.focus4trial.org/
   Google Scholar
• MODUL: A Multi-Center Study of Biomarker-Driven Therapy in Metastatic Colorectal Cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT02291289
   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
• Levine DM, Ek WE, Zhang R, et al. A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett’s esophagus. Nat Genet 2013;45(12):1487-93
   PubMed Web of Science ®Google Scholar
• Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med 2015;21(5):449-56
   PubMed Web of Science ®Google Scholar
• Gao Y, Chen Z, Li J, et al. Genetic landscape of esophageal squamous cell carcinoma. Nat Genet 2014;46(10):1097-102
   PubMed Web of Science ®Google Scholar
• Dulak AM, Stojanov P, Peng S, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet 2013;45(5):478-86
   PubMed Web of Science ®Google Scholar
• Song Y, Li L, Ou Y, et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature 2014;509(7498):91-5
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513(7517):202-9
   PubMed Web of Science ®Google Scholar