Molecular targeted therapy for the treatment of gastric cancer

Journal of Experimental and Clinical Cancer Research

Volumn 35, Issue 1, 2016, Pages

  Xu, Wenting ^a   Yang, Zhen ^a   Lu, Nonghua ^a  

^a NANCHANG UNIVERSITY   (China)

Author keywords

Gastric cancer; Molecular targeted therapy; Monoclonal antibody; Tyrosine kinase inhibitor

Indexed keywords

BEVACIZUMAB; BORTEZOMIB; CAPECITABINE; CETUXIMAB; CISPLATIN; CYCLOOXYGENASE 2 INHIBITOR; DOCETAXEL; EPIDERMAL GROWTH FACTOR; EPIRUBICIN; ERLOTINIB; FIGITUMUMAB; FLAVOPIRIDOL; FLUOROURACIL; GEFITINIB; LAPATINIB; MAMMALIAN TARGET OF RAPAMYCIN; MONOCLONAL ANTIBODY; OXALIPLATIN; PANITUMUMAB; PERTUZUMAB; PLACEBO; PROTEIN TYROSINE KINASE INHIBITOR; RAMUCIRUMAB; RILOTUMUMAB; SCATTER FACTOR RECEPTOR; SOMATOMEDIN RECEPTOR; SORAFENIB; SUNITINIB; TRASTUZUMAB; UNINDEXED DRUG; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; MTOR PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

ABDOMINAL PAIN; ACNE; ADVANCED CANCER; ANEMIA; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BLOOD TOXICITY; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER INCIDENCE; CANCER MORTALITY; CANCER PATIENT; CANCER PROGNOSIS; CANCER RECURRENCE; CANCER RESISTANCE; COLORECTAL CANCER; DIARRHEA; DRUG EFFICACY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG TOLERABILITY; EMBOLISM; ESOPHAGEAL ADENOCARCINOMA; ESOPHAGUS CANCER; EWING SARCOMA; FATIGUE; GASTROINTESTINAL SYMPTOM; GLIOBLASTOMA; HAND FOOT SYNDROME; HEART DISEASE; HEPATOBILIARY DISEASE; HUMAN; HYPERTENSION; HYPOKALEMIA; HYPOMAGNESEMIA; INTERSTITIAL LUNG DISEASE; KIDNEY CARCINOMA; LEUKOPENIA; MALIGNANT NEOPLASTIC DISEASE; MOLECULARLY TARGETED THERAPY; MUCOSA INFLAMMATION; MULTICENTER STUDY (TOPIC); NAUSEA; NEUTROPENIA; NON SMALL CELL LUNG CANCER; NONHUMAN; OPTIMAL DRUG DOSE; OVARY CANCER; OVERALL SURVIVAL; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; REVIEW; SIGNAL TRANSDUCTION; SKIN TOXICITY; STOMACH CANCER; STOMACH PERFORATION; STOMACH SURGERY; STOMATITIS; SURVIVAL TIME; THROMBOCYTOPENIA; TUMOR VASCULARIZATION; UNDIFFERENTIATED CARCINOMA; UNSPECIFIED SIDE EFFECT; VENOUS THROMBOEMBOLISM; VOMITING; WEAKNESS; ANTAGONISTS AND INHIBITORS; CELL CYCLE; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; METABOLISM; PROCEDURES; STOMACH NEOPLASMS;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; CELL CYCLE; CLINICAL TRIALS AS TOPIC; HUMANS; MOLECULAR TARGETED THERAPY; SIGNAL TRANSDUCTION; STOMACH NEOPLASMS; TOR SERINE-THREONINE KINASES;

EID: 84952926054     PISSN: None     EISSN: 17569966     Source Type: Journal    
DOI: 10.1186/s13046-015-0276-9     Document Type: Review

References (79)

1. Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol. 2013;107:230-6.
2. Rahman R, Asombang AW, Ibdah JA. Characteristics of gastric cancer in Asia. World J Gastroenterol. 2014;20:4483-90.
3. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69-90.
4. Riquelme I, Saavedra K, Espinoza JA, Weber H, Garcia P, Nervi B, et al. Molecular classification of gastric cancer: towards a pathway-driven targeted therapy. Oncotarget. 2015;6:24750-79.
5. Huang L, Chen T, Chen C, Chen S, Liu Y, Wu J, et al. Prognostic and predictive value of Phospho-p44/42 and pAKT in HER2-positive locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy. World J Surg Oncol. 2013;11:307.
6. Jacome AA, Wohnrath DR, Scapulatempo Neto C, Carneseca EC, Serrano SV, Viana LS, et al. Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors. Gastric Cancer. 2014;17:76-86.
7. Martin V, Landi L, Molinari F, Fountzilas G, Geva R, Riva A, et al. HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients. Br J Cancer. 2013;108:668-75.
8. Gonzaga IM, Soares-Lima SC, de Santos PT, Blanco TC, de Reis BS, Quintella DC, et al. Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas. BMC Cancer. 2012;12:569.
9. Kohrt HE, Colevas AD, Houot R, Weiskopf K, Goldstein MJ, Lund P, et al. Targeting CD137 enhances the efficacy of cetuximab. J Clin Invest. 2014;124:2668-82.
10. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337-45.
11. Pinto C, Di Fabio F, Siena S, Cascinu S, Rojas Llimpe FL, Ceccarelli C, 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;18:510-7.
12. Pinto C, Di Fabio F, Barone C, Siena S, Falcone A, Cascinu S, 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;101:1261-8.
13. Tebbutt NC, Parry MM, Zannino D, Strickland AH, Van Hazel GA, Pavlakis N, et al. Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophagogastric cancer: the AGITG ATTAX2 trial. Br J Cancer. 2013;108:771-4.
14. Brodowicz T, Ciuleanu TE, Radosavljevic D, Shacham-Shmueli E, Vrbanec D, Plate S, et al. FOLFOX4 plus cetuximab administered weekly or every second week in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer: a randomized phase II CECOG study. Ann Oncol. 2013;24:1769-77.
15. Kim C, Lee JL, Ryu MH, Chang HM, Kim TW, Lim HY, et al. A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Invest New Drugs. 2011;29:366-73.
16. Cappetta A, Lonardi S, Pastorelli D, Bergamo F, Lombardi G, Zagonel V. Advanced gastric cancer (GC) and cancer of the gastro-oesophageal junction (GEJ): focus on targeted therapies. Crit Rev Oncol Hematol. 2012;81:38-48.
17. Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, 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;14:490-9.
18. Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, 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;14:481-9.
19. Kim SY, Kim HP, Kim YJ, Oh do Y, Im SA, Lee D, et al. Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin. Int J Oncol. 2008;32:89-95.
20. 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.
21. Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004;5:317-28.
22. Yamashita-Kashima Y, Iijima S, Yorozu K, Furugaki K, Kurasawa M, Ohta M, et al. Pertuzumab in combination with trastuzumab shows significantly enhanced antitumor activity in HER2-positive human gastric cancer xenograft models. Clin Cancer Res. 2011;17:5060-70.
23. Oh DY, Bang YJ. Pertuzumab in Gastointestinal Cancer. Expert Opin Biol Ther. 2015.
24. Tateishi K, Ichiyama T, Hirai K, Agatsuma T, Koyama S, Hachiya T, et al. Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptor-mutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group study. Med Oncol. 2013;30:450.
25. Rojo F, Tabernero J, Albanell J, Van Cutsem E, Ohtsu A, Doi T, et al. Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma. J Clin Oncol. 2006;24:4309-16.
26. Adelstein DJ, Rodriguez CP, Rybicki LA, Ives DI, Rice TW. A phase II trial of gefitinib for recurrent or metastatic cancer of the esophagus or gastroesophageal junction. Invest New Drugs. 2012;30:1684-9.
27. Wang WP, Wang KN, Gao Q, Chen LQ. Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction. World J Surg Oncol. 2012;10:14.
28. Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF, et al. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006;24:4922-7.
29. Wainberg ZA, Anghel A, Desai AJ, Ayala R, Luo T, Safran B, 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;16:1509-9.
30. Hecht JR, Bang YJ, Qin S, Chung HC, Park JO, Jeziorski K, 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):abstr LBA4001.
31. Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, 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;32:2039-49.
32. Chen CT, Kim H, Liska D, Gao S, Christensen JG, Weiser MR. MET activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells. Mol Cancer Ther. 2012;11:660-9.
33. Trowe T, Boukouvala S, Calkins K, Cutler Jr RE, Fong R, Funke R, et al. EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation. Clin Cancer Res. 2008;14:2465-75.
34. Zhang X, Park JS, Park KH, Kim KH, Jung M, Chung HC, et al. PTEN deficiency as a predictive biomarker of resistance to HER2-targeted therapy in advanced gastric cancer. Oncology. 2015;88:76-85.
35. Grigore D, Simionescu CE, Stepan A, Margaritescu C, Balasoiu M, Georgescu CC, et al. Assessment of CD105, alpha-SMA and VEGF expression in gastric carcinomas. Rom J Morphol Embryol. 2013;54:701-7.
36. Tatli AM, Coskun HS, Uysal M, Arslan D, Sezgin Goksu S, Guenay Gunduz S, et al. Treatment with capecitabine + bevacizumab following induction treatment with FOLFIRI + bevacizumab in metastatic colorectal carcinoma. Int J Clin Exp Med. 2014;7:2191-6.
37. Loupakis F, Bria E, Vaccaro V, Cuppone F, Milella M, Carlini P, et al. Magnitude of benefit of the addition of bevacizumab to first-line chemotherapy for metastatic colorectal cancer: meta-analysis of randomized clinical trials. J Exp Clin Cancer Res. 2010;29:58.
38. Kim ES, Moon J, Herbst RS, Redman MW, Dakhil SR, Velasco Jr MR, et al. Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer: SWOG S0536. J Thorac Oncol. 2013;8:1519-28.
39. Hurvitz SA, Bosserman LD, Chan D, Hagenstad CT, Kass FC, Smith FP, et al. Cardiac safety results from a phase II, open-label, multicenter, pilot study of two docetaxel-based regimens plus bevacizumab for the adjuvant treatment of subjects with node-positive or high-risk node-negative breast cancer. Springerplus. 2014;3:244.
40. Cuppone F, Bria E, Vaccaro V, Puglisi F, Fabi A, Sperduti I, et al. Magnitude of risks and benefits of the addition of Bevacizumab to chemotherapy for advanced breast cancer patients: meta-regression analysis of randomized trials. J Exp Clin Cancer Res. 2011;30:54.
41. Flaherty KT, Manola JB, Pins M, McDermott DF, Atkins MB, Dutcher JJ, et al. BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma - A Trial of the ECOG-ACRIN Cancer Research Group (E2804). J Clin Oncol. 2015;33:2384-91.
42. Poveda AM, Selle F, Hilpert F, Reuss A, Savarese A, Vergote I, et al. Bevacizumab combined with weekly paclitaxel, Pegylated liposomal doxorubicin, or topotecan in platinum-resistant recurrent ovarian cancer: analysis by chemotherapy cohort of the randomized phase III AURELIA trial. J Clin Oncol. 2015;33:3836-8.
43. Kim A, Ueda Y, Naka T, Enomoto T. Therapeutic strategies in epithelial ovarian cancer. J Exp Clin Cancer Res. 2012;31:14.
44. Takano S, Ishikawa E, Nakai K, Matsuda M, Masumoto T, Yamamoto T, et al. Bevacizumab in Japanese patients with malignant glioma: from basic research to clinical trial. Onco Targets Ther. 2014;7:1551-62.
45. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, 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;29:3968-76.
46. Huang H, Zheng Y, Zhu J, Zhang J, Chen H, Chen X. An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients. PLoS One. 2014;9, e89960.
47. Van Cutsem E, de Haas S, Kang YK, Ohtsu A, Tebbutt NC, Ming Xu J, 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;30:2119-27.
48. 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.
49. 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.
50. Yi JH, Lee J, Lee J, Park SH, Park JO, Yim DS, 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;106:1469-74.
51. Gomez-Martin C, Salazar R, Montagut C, Gil-Martin M, Nunez JA, Puig M, et al. A phase I, dose-finding study of sunitinib combined with cisplatin and 5-fluorouracil in patients with advanced gastric cancer. Invest New Drugs. 2013;31:390-8.
52. Lee KW, Park SR, Oh DY, Park YI, Khosravan R, Lin X, et al. Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer. Invest New Drugs. 2013;31:1547-58.
53. Sun W, Powell M, O'Dwyer PJ, Catalano P, Ansari RH, Benson 3rd AB. 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;28:2947-51.
54. Duraiswamy J, Kaluza KM, Freeman GJ, Coukos G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res. 2013;73:3591-603.
55. Lim S, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development. 2013;140:3079-93.
56. Holkova B, Supko JG, Ames MM, Reid JM, Shapiro GI, Perkins EB, et al. A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Clin Cancer Res. 2013;19:1873-83.
57. Schwartz GK, Ilson D, Saltz L, O'Reilly E, Tong W, Maslak P, et al. Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma. J Clin Oncol. 2001;19:1985-92.
58. Xu L, Qu X, Luo Y, Zhang Y, Liu J, Qu J, et al. Epirubicin enhances TRAIL-induced apoptosis in gastric cancer cells by promoting death receptor clustering in lipid rafts. Mol Med Rep. 2011;4:407-11.
59. Sarlo C, Buccisano F, Maurillo L, Cefalo M, Di Caprio L, Cicconi L, et al. Phase II study of Bortezomib as a single agent in patients with previously untreated or relapsed/refractory acute myeloid leukemia ineligible for intensive therapy. Leuk Res Treatment. 2013;2013:705714.
60. Partyka R, Gonciarz M, Jalowiecki P, Kokocinska D, Byrczek T. VEGF and metalloproteinase 2 (MMP 2) expression in gastric cancer tissue. Med Sci Monit. 2012;18:BR130-4.
61. Wu T, Li Y, Lu J, Qiao Q, Bao G, Wang N, et al. Increased MMP-21 expression is associated with poor overall survival of patients with gastric cancer. Med Oncol. 2013;30:323.
62. He L, Chu D, Li X, Zheng J, Liu S, Li J, et al. Matrix metalloproteinase-14 is a negative prognostic marker for patients with gastric cancer. Dig Dis Sci. 2013;58:1264-70.
63. Zhang QW, Liu L, Chen R, Wei YQ, Li P, Shi HS, et al. Matrix metalloproteinase-9 as a prognostic factor in gastric cancer: a meta-analysis. Asian Pac J Cancer Prev. 2012;13:2903-8.
64. Bramhall SR, Hallissey MT, Whiting J, Scholefield J, Tierney G, Stuart RC, et al. Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial. Br J Cancer. 2002;86:1864-70.
65. Mariani M, McHugh M, Petrillo M, Sieber S, He S, Andreoli M, et al. HGF/c-Met axis drives cancer aggressiveness in the neo-adjuvant setting of ovarian cancer. Oncotarget. 2014;5:4855-67.
66. Hasenauer S, Malinger D, Koschut D, Pace G, Matzke A, von Au A, et al. Internalization of Met requires the co-receptor CD44v6 and its link to ERM proteins. PLoS One. 2013;8, e62357.
67. Kang YK, Muro K, Ryu MH, Yasui H, Nishina T, Ryoo BY, 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;32:355-61.
68. Wu JG, Yu JW, Wu HB, Zheng LH, Ni XC, Li XQ, et al. Expressions and clinical significances of c-MET, p-MET and E2f-1 in human gastric carcinoma. BMC Res Notes. 2014;7:6.
69. Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, 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;15:1007-18.
70. Cunningham D, Tebbutt NC, Davidenko I, Murad AM, AI-Batran SE, IIson DH, 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):abstr 4000.
71. Kwak F. Clinical activity observed in a phase I dose escalation trialof anoral c-met and ALK inhibitor. J Clin Oncol. 2009;27 Suppl:abstr 15.
72. Sasore T, Kennedy B. Deciphering combinations of PI3K/AKT/mTOR pathway drugs augmenting anti-angiogenic efficacy in vivo. PLoS One. 2014;9, e105280.
73. Yu G, Wang J, Chen Y, Wang X, Pan J, Li G, et al. Overexpression of phosphorylated mammalian target of rapamycin predicts lymph node metastasis and prognosis of chinese patients with gastric cancer. Clin Cancer Res. 2009;15:1821-9.
74. Alvarado Y, Mita MM, Vemulapalli S, Mahalingam D, Mita AC. Clinical activity of mammalian target of rapamycin inhibitors in solid tumors. Target Oncol. 2011;6:69-94.
75. 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.
76. Ganesh R, Marks DJ, Sales K, Winslet MC, Seifalian AM. Cyclooxygenase/lipoxygenase shunting lowers the anti-cancer effect of cyclooxygenase-2 inhibition in colorectal cancer cells. World J Surg Oncol. 2012;10:200.
77. Juergens H, Daw NC, Geoerger B, Ferrari S, Villarroel M, Aerts I, et al. Preliminary efficacy of the anti-insulin-like growth factor type 1 receptor antibody figitumumab in patients with refractory Ewing sarcoma. J Clin Oncol. 2011;29:4534-40.
78. Goto Y, Sekine I, Tanioka M, Shibata T, Tanai C, Asahina H, et al. Figitumumab combined with carboplatin and paclitaxel in treatment-naive Japanese patients with advanced non-small cell lung cancer. Invest New Drugs. 2012;30:1548-56.
79. Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, et al. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014;32:2059-66.