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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 660 - 665 (6page)
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초록· 키워드
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Human epidermal growth factor receptor 2 (HER2) inhibitors, such as trastuzumab and lapatinib are used to treat HER2-positive breast and gastric cancers. However, as with other targeted therapies, intrinsic or acquired resistance to HER2 inhibitors presents unresolved therapeutic problems for HER2-positive gastric cancer. The present study describes investigations with AUY922, a heat shock protein 90 (HSP90) inhibitor, in primary lapatinib-resistant (ESO26 and OE33) and lapatinib-sensitive gastric cancer cells (OE19, N87, and SNU-216) harboring HER2 amplification/over-expression. In order to investigate whether AUY922 could overcome intrinsic and acquired resistance to HER2 inhibitors in HER2-positive gastric cancer, we generated lapatinib-resistant gastric cancer cell lines (OE19/LR and N87/LR) by continuous exposure to lapatinib in vitro. We found that activation of HER2 and protein kinase B (AKT) were key factors in inducing intrinsic and acquired lapatinib-resistant gastric cancer cell lines, and that AUY922 effectively suppressed activation of both HER2 and AKT in acquired lapatinib-resistant gastric cancer cell lines. In conclusion, AUY922 showed a synergistic anti-cancer effect with lapatinib and sensitized gastric cancer cells with intrinsic resistance to lapatinib. Dual inhibition of the HSP90 and HER2 signaling pathways could represent a potent therapeutic strategy to treat HER2-positive gastric cancer with intrinsic and acquired resistance to lapatinib.
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등록된 정보가 없습니다.
참고문헌 (34)
참고문헌 신청
Bray F / 2018 / Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185 countries / CA Cancer J Clin 68:394~424
Glimelius B / 1997 / Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer / Ann Oncol 8:163~168
Cunningham D / 2008 / Capecitabine and oxaliplatin for advanced esophagogastric cancer / N Engl J Med 358:36~46
Kang YK / 2009 / Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial / Ann Oncol 20:666~673
Bang YJ / 2010 / 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 376:687~697
Glimelius B / 1997 / Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer / Ann Oncol 8:163~168
Cunningham D / 2008 / Capecitabine and oxaliplatin for advanced esophagogastric cancer / N Engl J Med 358:36~46
Kang YK / 2009 / Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial / Ann Oncol 20:666~673
Bang YJ / 2010 / 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 376:687~697
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