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Erschienen in: Journal of Cancer Research and Clinical Oncology 7/2009

01.07.2009 | Review

Gastric cancer in the era of molecularly targeted agents: current drug development strategies

verfasst von: Hendrik-Tobias Arkenau

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2009

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Abstract

Gastric cancer is the second most common cause of cancer death worldwide with approximately one million cases diagnosed annually. Despite considerable improvements in surgical techniques, innovations in clinical diagnostics and the development of new chemotherapy regimens, the clinical outcome for patients with advanced gastric cancer and cancer of the GEJ is generally poor with 5-year survival rates ranging between 5 and 15%. The understanding of cancer relevant events has resulted in new therapeutic strategies, particularly in developing of new molecular targeted agents. These agents have the ability to target a variety of cancer relevant receptors and downstream pathways including the epidermal growth factor receptor (EGFR), the vascular endothelial growth factor receptor (VEGFR), the insulin-like growth factor receptor (IGFR), the c-Met pathway, cell-cycle pathways, and down-stream signalling pathways such as the Akt-PI3k-mTOR pathway. In the era of new molecularly targeted agents this review focuses on recent developments of targeting relevant pathways involved in gastric cancer and cancer of the GEJ.
Literatur
Zurück zum Zitat Attard G, Fong PC, Molife R et al (2006) Phase I trial involving the pharmacodynamic (PD) study of circulating tumour cells, of CP-751, 871 (C), a monoclonal antibody against the insulin-like growth factor 1 receptor (IGF-1R), with docetaxel (D) in patients (p) with advanced cancer. J Clin Oncol 24:3023 Attard G, Fong PC, Molife R et al (2006) Phase I trial involving the pharmacodynamic (PD) study of circulating tumour cells, of CP-751, 871 (C), a monoclonal antibody against the insulin-like growth factor 1 receptor (IGF-1R), with docetaxel (D) in patients (p) with advanced cancer. J Clin Oncol 24:3023
Zurück zum Zitat Bae SH, Ryoo HM, Kim MK et al (2008) Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapeutic agents in gastric cancer cell lines. Oncol Rep 19(4):1027–1032PubMed Bae SH, Ryoo HM, Kim MK et al (2008) Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapeutic agents in gastric cancer cell lines. Oncol Rep 19(4):1027–1032PubMed
Zurück zum Zitat Bang Y, Chung H, Sawaki A et al (2008) HER2-positivity rates in advanced gastric cancer (GC): results from a large international phase III trial. J Clin Oncol 26:4526 Bang Y, Chung H, Sawaki A et al (2008) HER2-positivity rates in advanced gastric cancer (GC): results from a large international phase III trial. J Clin Oncol 26:4526
Zurück zum Zitat Carpenter G, Cohen S (1990) Epidermal growth factor. J Biol Chem 265:7709–7712PubMed Carpenter G, Cohen S (1990) Epidermal growth factor. J Biol Chem 265:7709–7712PubMed
Zurück zum Zitat Cauwe B, Van den Steen PE, Opdenakker G (2007) The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol 42(3):113–185. doi:10.1080/10409230701340019 PubMedCrossRef Cauwe B, Van den Steen PE, Opdenakker G (2007) The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol 42(3):113–185. doi:10.​1080/​1040923070134001​9 PubMedCrossRef
Zurück zum Zitat Cejka D, Preusser M, Woehrer A et al. (2008) Everolimus (RAD001) and anti-angiogenic cyclophosphamide show long-term control of gastric cancer growth in vivo. Cancer Biol Ther 7(9) (epub ahead of print) Cejka D, Preusser M, Woehrer A et al. (2008) Everolimus (RAD001) and anti-angiogenic cyclophosphamide show long-term control of gastric cancer growth in vivo. Cancer Biol Ther 7(9) (epub ahead of print)
Zurück zum Zitat Cheema HS, Motwani MV et al. (2004) Suberoylanilide Hydroxamic Acid (SAHA), a histone deacetylase (HDAC) inhibitor, induces a unique mitotic effect and potentiates flavopiridol (F) induced apoptosis. Proc Am Assoc Cancer Res 45: 2443 Cheema HS, Motwani MV et al. (2004) Suberoylanilide Hydroxamic Acid (SAHA), a histone deacetylase (HDAC) inhibitor, induces a unique mitotic effect and potentiates flavopiridol (F) induced apoptosis. Proc Am Assoc Cancer Res 45: 2443
Zurück zum Zitat Cohenuram MK, Lacy J (2008) FOLFOX6 and bevacizumab (FOLFOX6/B) for metastatic esophageal (E), gastroesophageal (GE), and gastric (G) adenocarcinoma: a single institution’s initial clinical experience. Proc GI ASCO: 74 Cohenuram MK, Lacy J (2008) FOLFOX6 and bevacizumab (FOLFOX6/B) for metastatic esophageal (E), gastroesophageal (GE), and gastric (G) adenocarcinoma: a single institution’s initial clinical experience. Proc GI ASCO: 74
Zurück zum Zitat Cortés-Funes H, Rivera F, Alés I et al (2007) Phase II of trastuzumab and cisplatin in patients (pts) with advanced gastric cancer (AGC) with HER2/neu overexpression/amplification. J Clin Oncol 25:4613 Cortés-Funes H, Rivera F, Alés I et al (2007) Phase II of trastuzumab and cisplatin in patients (pts) with advanced gastric cancer (AGC) with HER2/neu overexpression/amplification. J Clin Oncol 25:4613
Zurück zum Zitat Dar AA, Zaika A, Piazuela MB et al (2008) Frequent overexpression of aurora kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer 112(8):1688–1698. doi:10.1002/cncr.23371 PubMedCrossRef Dar AA, Zaika A, Piazuela MB et al (2008) Frequent overexpression of aurora kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer 112(8):1688–1698. doi:10.​1002/​cncr.​23371 PubMedCrossRef
Zurück zum Zitat de Mingo M, Morán A, Sánchez-Pernaute A et al (2007) Expression of MMP-9 and TIMP-1 as prognostic markers in gastric carcinoma. Hepatogastroenterology 54(73):315–319PubMed de Mingo M, Morán A, Sánchez-Pernaute A et al (2007) Expression of MMP-9 and TIMP-1 as prognostic markers in gastric carcinoma. Hepatogastroenterology 54(73):315–319PubMed
Zurück zum Zitat Eskens FA, Mom CH, Planting AS et al (2008) A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer 98(1):80–85. doi:10.1038/sj.bjc.6604108 PubMedCrossRef Eskens FA, Mom CH, Planting AS et al (2008) A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer 98(1):80–85. doi:10.​1038/​sj.​bjc.​6604108 PubMedCrossRef
Zurück zum Zitat Haluska P, Shaw H, Batzel GN et al (2007) Phase I dose escalation study of the anti-IGF-1R monoclonal antibody CP-751, 871 in patients with refractory solid tumors. J Clin Oncol 25:3586 Haluska P, Shaw H, Batzel GN et al (2007) Phase I dose escalation study of the anti-IGF-1R monoclonal antibody CP-751, 871 in patients with refractory solid tumors. J Clin Oncol 25:3586
Zurück zum Zitat Hammad N, Philip PA, Shields AF et al. (2008) A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and gastroesophageal junction (GEJ) cancer. Proc GI ASCO: 30 Hammad N, Philip PA, Shields AF et al. (2008) A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and gastroesophageal junction (GEJ) cancer. Proc GI ASCO: 30
Zurück zum Zitat Hattori Y, Itoh H, Uchino S et al (1996) Immunohistochemical detection of K-sam protein in stomach cancer. Clin Cancer Res 2(8):1373–1381PubMed Hattori Y, Itoh H, Uchino S et al (1996) Immunohistochemical detection of K-sam protein in stomach cancer. Clin Cancer Res 2(8):1373–1381PubMed
Zurück zum Zitat Hecht JR, Urba SG, Koehler M et al. (2008) Lapatinib monotherapy in recurrent upper gastrointestinal malignancy: phase II efficacy and biomarker analyses. Proc GI ASCO: 43 Hecht JR, Urba SG, Koehler M et al. (2008) Lapatinib monotherapy in recurrent upper gastrointestinal malignancy: phase II efficacy and biomarker analyses. Proc GI ASCO: 43
Zurück zum Zitat Hecht JR, Mitchell E, Chidiac T et al (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27(5):672–680. doi:10.1200/JCO.2008.19.8135 PubMedCrossRef Hecht JR, Mitchell E, Chidiac T et al (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27(5):672–680. doi:10.​1200/​JCO.​2008.​19.​8135 PubMedCrossRef
Zurück zum Zitat Hinoda Y, Sasaki S, Ishida T et al (2004) Monoclonal antibodies as effective therapeutic agents for solid tumors. Cancer Sci 96:443–446 Hinoda Y, Sasaki S, Ishida T et al (2004) Monoclonal antibodies as effective therapeutic agents for solid tumors. Cancer Sci 96:443–446
Zurück zum Zitat Hirata A, Ogawa S, Kometani T et al (2002) ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res 62(9):2554–2560PubMed Hirata A, Ogawa S, Kometani T et al (2002) ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res 62(9):2554–2560PubMed
Zurück zum Zitat Iqbal S, Goldman B, Lenz HJ et al (2007) S0413: a phase II SWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer. J Clin Oncol 25:4621 Iqbal S, Goldman B, Lenz HJ et al (2007) S0413: a phase II SWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer. J Clin Oncol 25:4621
Zurück zum Zitat Jang YJ, Kim YS, Kim WH et al (2006) Oncogenic effect of Polo-like kinase 1 expression in human gastric carcinomas. Int J Cancer 29(3):589–594 Jang YJ, Kim YS, Kim WH et al (2006) Oncogenic effect of Polo-like kinase 1 expression in human gastric carcinomas. Int J Cancer 29(3):589–594
Zurück zum Zitat Jhawer MP, Ilson D, Robinson E et al. (2008) Interim results of a phase II study of modified docetaxel, cisplatin, fluorouracil (mDCF), and bevacizumab (BEV) in patients with metastatic gastroesophageal (GE) adenocarcinoma. Proc GI ASCO: 109 Jhawer MP, Ilson D, Robinson E et al. (2008) Interim results of a phase II study of modified docetaxel, cisplatin, fluorouracil (mDCF), and bevacizumab (BEV) in patients with metastatic gastroesophageal (GE) adenocarcinoma. Proc GI ASCO: 109
Zurück zum Zitat Jhawer MP, Kindler HL, Wainberg ZA et al (2008b) Preliminary activity of XL880, a dual MET/VEGFR2 inhibitor, in MET amplified poorly differentiated gastric cancer (PDGC): interim results of a multicenter phase II study. J Clin Oncol 26:4572. doi:10.1200/JCO.2007.15.5655 CrossRef Jhawer MP, Kindler HL, Wainberg ZA et al (2008b) Preliminary activity of XL880, a dual MET/VEGFR2 inhibitor, in MET amplified poorly differentiated gastric cancer (PDGC): interim results of a multicenter phase II study. J Clin Oncol 26:4572. doi:10.​1200/​JCO.​2007.​15.​5655 CrossRef
Zurück zum Zitat Kamada K, Yamada Y, Hirao T et al (2004) Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. Oncol Rep 12(3):593–599PubMed Kamada K, Yamada Y, Hirao T et al (2004) Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. Oncol Rep 12(3):593–599PubMed
Zurück zum Zitat Kim JW, Kim HP, Im SA et al. (2008) The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines. Cancer Lett (e-pub ahead of print) Kim JW, Kim HP, Im SA et al. (2008) The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines. Cancer Lett (e-pub ahead of print)
Zurück zum Zitat Lang SA, Klein D, Moser C et al (2007a) Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo. Mol Cancer Ther 6(3):1123–1132. doi:10.1158/1535-7163.MCT-06-0628 PubMedCrossRef Lang SA, Klein D, Moser C et al (2007a) Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo. Mol Cancer Ther 6(3):1123–1132. doi:10.​1158/​1535-7163.​MCT-06-0628 PubMedCrossRef
Zurück zum Zitat Lang SA, Gaumann A, Koehl GE et al (2007b) Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer 120(8):1803–1810. doi:10.1002/ijc.22442 PubMedCrossRef Lang SA, Gaumann A, Koehl GE et al (2007b) Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer 120(8):1803–1810. doi:10.​1002/​ijc.​22442 PubMedCrossRef
Zurück zum Zitat Lordick F, Lorenzen S, Hegewisch-Becker S et al (2007) Cetuximab plus weekly oxaliplatin/5FU/FA (FUFOX) in 1st line metastatic gastric cancer. Final results from a multicenter phase II study of the AIO upper GI study group. J Clin Oncol 26:4526 Lordick F, Lorenzen S, Hegewisch-Becker S et al (2007) Cetuximab plus weekly oxaliplatin/5FU/FA (FUFOX) in 1st line metastatic gastric cancer. Final results from a multicenter phase II study of the AIO upper GI study group. J Clin Oncol 26:4526
Zurück zum Zitat Macarulla T, Ramos FJ, Tabernero J (2008) Aurora kinase family: a new target for anticancer drug. Recent Patents Anticancer Drug Discov 3(2):114–122CrossRef Macarulla T, Ramos FJ, Tabernero J (2008) Aurora kinase family: a new target for anticancer drug. Recent Patents Anticancer Drug Discov 3(2):114–122CrossRef
Zurück zum Zitat Marks PA, Jiang X (2005) Histone deacetylase inhibitors in programmed cell death and cancer therapy. Cell Cycle 4(4):549–551PubMed Marks PA, Jiang X (2005) Histone deacetylase inhibitors in programmed cell death and cancer therapy. Cell Cycle 4(4):549–551PubMed
Zurück zum Zitat Matsubara J, Yamada Y, Hirashima Y et al (2008) Impact of insulin-like growth factor type 1 receptor, epidermal growth factor receptor, and HER2 expressions on outcomes of patients with gastric cancer. Clin Cancer Res 14(10):3022–3029. doi:10.1158/1078-0432.CCR-07-1898 PubMedCrossRef Matsubara J, Yamada Y, Hirashima Y et al (2008) Impact of insulin-like growth factor type 1 receptor, epidermal growth factor receptor, and HER2 expressions on outcomes of patients with gastric cancer. Clin Cancer Res 14(10):3022–3029. doi:10.​1158/​1078-0432.​CCR-07-1898 PubMedCrossRef
Zurück zum Zitat McCarty MF, Wey J, Stoeltzing O et al (2004) ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor with additional activity against epidermal growth factor receptor tyrosine kinase, inhibits orthotopic growth and angiogenesis of gastric cancer. Mol Cancer Ther 3(9):1041–1048PubMed McCarty MF, Wey J, Stoeltzing O et al (2004) ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor with additional activity against epidermal growth factor receptor tyrosine kinase, inhibits orthotopic growth and angiogenesis of gastric cancer. Mol Cancer Ther 3(9):1041–1048PubMed
Zurück zum Zitat Moehler M, Hartmann JT, Lordick F et al. (2009) Sunitinib in patients with chemorefractory metastatic gastric cancer: preliminary results of an open-label, prospective non-randomised multicentre AIO Phase II trial. Proc GI ASCO: 61 Moehler M, Hartmann JT, Lordick F et al. (2009) Sunitinib in patients with chemorefractory metastatic gastric cancer: preliminary results of an open-label, prospective non-randomised multicentre AIO Phase II trial. Proc GI ASCO: 61
Zurück zum Zitat Muro K, Boku N, Yamada Y et al (2008) Multicenter phase II study of RAD001 for previously treated metastatic gastric cancer (MGC): preliminary results. J Clin Oncol 26:4541 Muro K, Boku N, Yamada Y et al (2008) Multicenter phase II study of RAD001 for previously treated metastatic gastric cancer (MGC): preliminary results. J Clin Oncol 26:4541
Zurück zum Zitat Nakajima M, Sawada H, Yamada Y et al (2000) The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 85:1894–1902 Nakajima M, Sawada H, Yamada Y et al (2000) The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 85:1894–1902
Zurück zum Zitat Ocean AJ, Schnoll-Sussman F, Chen X et al. (2007) Phase II study of PS-341 (VELCADE, bortezomib) with or without irinotecan in patients (pts) with advanced gastric adenocarcinomas (AGA). Proc GI ASCO: 45 Ocean AJ, Schnoll-Sussman F, Chen X et al. (2007) Phase II study of PS-341 (VELCADE, bortezomib) with or without irinotecan in patients (pts) with advanced gastric adenocarcinomas (AGA). Proc GI ASCO: 45
Zurück zum Zitat Pinto C, Di Fabio F, Siena S et al (2007) Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 18(3):510–517. doi:10.1093/annonc/mdl459 PubMedCrossRef Pinto C, Di Fabio F, Siena S et al (2007) Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 18(3):510–517. doi:10.​1093/​annonc/​mdl459 PubMedCrossRef
Zurück zum Zitat Pinto C, Di Fabio F, Barone C et al. (2008) Phase II study of cetuximab in combination with cisplatin/docetaxel as first-line treatment in patients with unresectable/metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (DOCETUX Study): preliminary results. Proc GI ASCO: 34 Pinto C, Di Fabio F, Barone C et al. (2008) Phase II study of cetuximab in combination with cisplatin/docetaxel as first-line treatment in patients with unresectable/metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (DOCETUX Study): preliminary results. Proc GI ASCO: 34
Zurück zum Zitat Presta LG, Chen H, O’Connor SJ et al (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593–4599PubMed Presta LG, Chen H, O’Connor SJ et al (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593–4599PubMed
Zurück zum Zitat Rao S, Starling N, Cunningham D et al. (2008) Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer. Br J Cancer (epub ahead of print) Rao S, Starling N, Cunningham D et al. (2008) Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer. Br J Cancer (epub ahead of print)
Zurück zum Zitat Saltz LB, Lenz HJ, Kindler HL et al (2007) Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 Study. J Clin Oncol 25:4557–4561. doi:10.1200/JCO.2007.12.0949 PubMedCrossRef Saltz LB, Lenz HJ, Kindler HL et al (2007) Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 Study. J Clin Oncol 25:4557–4561. doi:10.​1200/​JCO.​2007.​12.​0949 PubMedCrossRef
Zurück zum Zitat Schwartz GK, Ilson D, Saltz L et al (2001) Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma. J Clin Oncol 19(7):1985–1992PubMed Schwartz GK, Ilson D, Saltz L et al (2001) Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma. J Clin Oncol 19(7):1985–1992PubMed
Zurück zum Zitat Shah MA, Ramanathan RK, Ilson DH et al (2006) Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 24(33):5201–5206. doi:10.1200/JCO.2006.08.0887 PubMedCrossRef Shah MA, Ramanathan RK, Ilson DH et al (2006) Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 24(33):5201–5206. doi:10.​1200/​JCO.​2006.​08.​0887 PubMedCrossRef
Zurück zum Zitat Stein A, Al-Batran SE, Arnold D et al. (2007) Cetuximab with irinotecan as salvage therapy in heavily pretreated patients with metastatic gastric cancer. Proc GI ASCO: 47 Stein A, Al-Batran SE, Arnold D et al. (2007) Cetuximab with irinotecan as salvage therapy in heavily pretreated patients with metastatic gastric cancer. Proc GI ASCO: 47
Zurück zum Zitat Sun W, Powell ME, O’Dwyer P et al (2008) A phase II study: combination of sorafenib with docetaxel and cisplatin in the treatment of metastatic or advanced unresectable gastric and gastroesophageal junction (GEJ) adenocarcinoma (ECOG 5203). J Clin Oncol 26:4535CrossRef Sun W, Powell ME, O’Dwyer P et al (2008) A phase II study: combination of sorafenib with docetaxel and cisplatin in the treatment of metastatic or advanced unresectable gastric and gastroesophageal junction (GEJ) adenocarcinoma (ECOG 5203). J Clin Oncol 26:4535CrossRef
Zurück zum Zitat Tahara E (2004) Genetic pathways of two types of gastric cancer. IARC Sci Publ 157:327–349PubMed Tahara E (2004) Genetic pathways of two types of gastric cancer. IARC Sci Publ 157:327–349PubMed
Zurück zum Zitat Tanner M, Hollmen M, Junttila TT et al (2005) Amplification of HER-2 in gastric carcinoma: association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 16:273–278. doi:10.1093/annonc/mdi064 PubMedCrossRef Tanner M, Hollmen M, Junttila TT et al (2005) Amplification of HER-2 in gastric carcinoma: association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 16:273–278. doi:10.​1093/​annonc/​mdi064 PubMedCrossRef
Zurück zum Zitat Tebbutt NC, Sourjina T, Strickland AH et al (2008) ATTAX2: docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophago-gastric cancer—final results of a multicentre phase II trial by the AGITG. J Clin Oncol 26:15554 Tebbutt NC, Sourjina T, Strickland AH et al (2008) ATTAX2: docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophago-gastric cancer—final results of a multicentre phase II trial by the AGITG. J Clin Oncol 26:15554
Zurück zum Zitat Tol J, Koopman M, Cats A et al. (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360(6):563–572 Tol J, Koopman M, Cats A et al. (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360(6):563–572
Zurück zum Zitat Tortora G, Ciardiello F, Gasparini G (2008) Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications. Nat Clin Pract Oncol 5(9):521–530. doi:10.1038/ncponc1161 PubMedCrossRef Tortora G, Ciardiello F, Gasparini G (2008) Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications. Nat Clin Pract Oncol 5(9):521–530. doi:10.​1038/​ncponc1161 PubMedCrossRef
Zurück zum Zitat Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664. doi:10.1200/JCO.2006.08.1620 PubMedCrossRef Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664. doi:10.​1200/​JCO.​2006.​08.​1620 PubMedCrossRef
Zurück zum Zitat Wang HK (2001) Flavopiridol. National Cancer Institute. Curr Opin Invest Drugs 2(8):1149–1155 Wang HK (2001) Flavopiridol. National Cancer Institute. Curr Opin Invest Drugs 2(8):1149–1155
Zurück zum Zitat Wang WH, Huang JQ, Zheng GF et al (2003) Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a systematic review and meta-analysis. J Natl Cancer Inst 95(23):1784–1791PubMed Wang WH, Huang JQ, Zheng GF et al (2003) Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a systematic review and meta-analysis. J Natl Cancer Inst 95(23):1784–1791PubMed
Zurück zum Zitat Woell E, Greil R, Eisterer W et al (2008) Oxaliplatin, irinotecan and cetuximab in advanced gastric cancer: first results of a multicenter phase II trial (AGMT Gastric-2). J Clin Oncol 26:15587 Woell E, Greil R, Eisterer W et al (2008) Oxaliplatin, irinotecan and cetuximab in advanced gastric cancer: first results of a multicenter phase II trial (AGMT Gastric-2). J Clin Oncol 26:15587
Zurück zum Zitat Yap TA, Harris D, Barriuso J et al (2008) Phase I trial to determine the dose range for the c-Met inhibitor ARQ 197 that inhibits c-Met and FAK phosphorylation, when administered by an oral twice-a-day schedule. J Clin Oncol 26:3584 Yap TA, Harris D, Barriuso J et al (2008) Phase I trial to determine the dose range for the c-Met inhibitor ARQ 197 that inhibits c-Met and FAK phosphorylation, when administered by an oral twice-a-day schedule. J Clin Oncol 26:3584
Zurück zum Zitat Zuo DS, Dai J, Bo AH et al (2003) Significance of expression of heat shock protein90alpha in human gastric cancer. World J Gastroenterol 9(11):2616–2618PubMed Zuo DS, Dai J, Bo AH et al (2003) Significance of expression of heat shock protein90alpha in human gastric cancer. World J Gastroenterol 9(11):2616–2618PubMed
Metadaten
Titel
Gastric cancer in the era of molecularly targeted agents: current drug development strategies
verfasst von
Hendrik-Tobias Arkenau
Publikationsdatum
01.07.2009
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-009-0583-7

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