Journal
SCIENTIFIC REPORTS
Volume 3, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep02669
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan [24591165]
- Funding Program for Next Generation World-Leading Researchers (NEXT Program), Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST JST)
- Special Coordination Funds for Promoting Science and Technology, Japan
- Grants-in-Aid for Scientific Research [25670143, 24591165] Funding Source: KAKEN
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Small-cell lung cancer (SCLC) easily recurs with a multidrug resistant phenotype. However, standard therapeutic strategies for relapsed SCLC remain unestablished. We found that human epidermal growth factor receptor 2 (HER2) is not only expressed in pretreated human SCLC specimens, but is also upregulated when HER2-positive SCLC cells acquire chemoresistance. Trastuzumab induced differential levels of antibody-dependent cell-mediated cytotoxicity (ADCC) to HER2-positive SCLC cells. Furthermore, as a mechanism of the differential levels of ADCC, we have revealed that coexpression of intracellular adhesion molecule (ICAM)-1 on SCLC cells is essential to facilitate and accelerate the trastuzumab-mediated ADCC. Although SN-38-resistant SCLC cells lacking ICAM-1 expression were still refractory to trastuzumab, their in vivo growth was significantly suppressed by bevacizumab treatment due to dependence on their distinctive and abundant production of vascular endothelial growth factor. Collectively, stepwise treatment with trastuzumab and bevacizumab is promising for the treatment of chemoresistant SCLC.
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