Combining trastuzumab and cetuximab combats trastuzumab-resistant gastric cancer by effective inhibition of EGFR/ErbB2 heterodimerization and signaling

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• 作者：Lei Zheng (1) (2)
  Wenlong Tan (1) (3)
  Jinrong Zhang (1)
  Dongcai Yuan (4)
  Jingci Yang (5)
  Hongmei Liu (1)
  
• 关键词：ErbB2 ; EGFR ; Trastuzumab ; Cetuximab ; NCI ; N87 ; Trastuzumab ; resistant
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：63
• 期：6
• 页码：581-586
• 全文大小：
• 参考文献：1. Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ (2009) Gastric cancer. Lancet 374:477鈥?90 CrossRef
  2. Hofmann M, Stoss O, Shi D, B眉ttner R, van de Vijver M, Kim W, Ochiai A, R眉schoff J, Henkel T (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797鈥?05 CrossRef
  3. Tanner M, Hollm茅n M, Junttila TT, Kapanen AI, Tommola S, Soini Y, Helin H, Salo J, Joensuu H, Sihvo E, Elenius K, Isola J (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鈥?78 CrossRef
  4. Matsubara J, Yamada Y, Nakajima TE, Kato K, Hamaguchi T, Shirao K, Shimada Y, Shimoda T (2008) Clinical significance of insulin-like growth factor type 1 receptor and epidermal growth factor receptor in patients with advanced gastric cancer. Oncology 74:76鈥?3 CrossRef
  5. Hudis CA (2007) Trastuzumab: mechanism of action and use in clinical practice. N Engl J Med 357:39鈥?1 CrossRef
  6. Nahta R, Esteva FJ (2006) HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Res 8:215 CrossRef
  7. Narayan M, Wilken JA, Harris LN, Baron AT, Kimbler KD, Maihle NJ (2009) Trastuzumab-induced HER reprogramming in 鈥渞esistant鈥?breast carcinoma cells. Cancer Res 69:2191鈥?194 CrossRef
  8. Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R, Stegh AH, Bradner JE, Ligon KL, Brennan C, Chin L, DePinho RA (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318:287鈥?90 CrossRef
  9. Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, Xiong Y, Tseng LM, Li SH, Ding Z, Sahin AA, Esteva FJ, Hortobagyi GN, Yu D (2011) Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med 17:461鈥?69 CrossRef
  10. Mendelsohn J (2002) Targeting the epidermal growth factor receptor for cancer therapy. J Clin Oncol 20:1S鈥?3S
  11. Schmitz KR, Ferguson KM (2009) Interaction of antibodies with ErbB receptor extracellular regions. Exp Cell Res 315:659鈥?70 CrossRef
  12. Patel D, Bassi R, Hooper A, Prewett M, Hicklin DJ, Kang X (2009) Anti-epidermal growth factor receptor monoclonal antibody cetuximab inhibits EGFR/HER-2 heterodimerization and activation. Int J Oncol 34:25鈥?2
  13. Kondo N, Tsukuda M, Sakakibara A, Takahashi H, Hyakusoku H, Komatsu M, Niho T, Nakazaki K, Toth G (2012) Combined molecular targeted drug therapy for EGFR and HER-2 in head and neck squamous cell carcinoma cell lines. Int J Oncol 40:1805鈥?812
  14. Larbouret C, Gaborit N, Chard猫s T, Coelho M, Campigna E, Bascoul-Mollevi C, Mach JP, Azria D, Robert B, P猫legrin A (2012) In pancreatic carcinoma, dual EGFR/HER2 targeting with cetuximab/trastuzumab is more effective than treatmentwith trastuzumab/erlotinib or lapatinib alone implication of receptors鈥?down-regulation and dimers鈥?disruption. Neoplasia 14:121鈥?30
  15. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX (2009) Ligand-independent HER2/HER3/PI3聽K complex is disrupted by trastuzumab and is effectively inhibited by thePI3聽K inhibitor GDC-0941. Cancer Cell 15:429鈥?40 CrossRef
  
• 作者单位：Lei Zheng (1) (2)
  Wenlong Tan (1) (3)
  Jinrong Zhang (1)
  Dongcai Yuan (4)
  Jingci Yang (5)
  Hongmei Liu (1)
  
  1. Central Laboratory, Harrison International Peace Hospital, 180 Ren Min East Road, Hengshui, 053000, Hebei, People鈥檚 Republic of China
  2. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People鈥檚 Republic of China
  3. Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, People鈥檚 Republic of China
  4. Department of Neurology, Harrison International Peace Hospital, Hengshui, People鈥檚 Republic of China
  5. Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang, People鈥檚 Republic of China
  
• ISSN：1432-0851

文摘

The anti-ErbB2 antibody trastuzumab has currently been approved for ErbB2-positive gastric cancer. Despite the effectiveness of trastuzumab, resistance is common. Thus, there is an urgent need to overcome trastuzumab resistance. Here, we obtain a trastuzumab-resistant cell line, which is derived from the human gastric cancer NCI-N87 cell line, by modeling the development of acquired resistance in patients. Our data show that combining trastuzumab and cetuximab leads to a significant decrease in EGFR/ErbB2 heterodimers and signaling compared with either antibody alone, and the combination results in greater antitumor activity against the trastuzumab-resistant NCI-N87 cell line, both in vitro and in vivo, suggesting that a combined EGFR/ErbB2 inhibition may overcome trastuzumab resistance.