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- W2892018778 abstract "e20572 Background: Lung cancer is a leading cause of cancer death worldwide. The EGFR mutation-positive patients of lung adenocarcinoma had dramatic response to EGFR tyrosine kinase inhibitors (TKIs). However, acquired drug resistance developed invariably after one year treatment course of EGFR TKI. IGFBP-7, a secreted 31 kDa protein, exhibits low affinity for IGF but binds strongly to insulin. No previous studies had been mentioned the correlation between the protein and acquired EGFR TKI resistance. Methods: cDNA microarray was used to screen differentially expressed genes between EGFR TKI-sensitive (PC9 and HCC827) and acquired EGFR TKIs-resistance cell lines (PC9/gef and HCC827/gef). The expression levels of the screened genes were validated by RT -PCR and Western blot analysis. Molecular manipulations (silencing or overexpression) were performed to investigate the effects of IGFBP-7 on gefitinib resistance in vitro. In addition, clinical specimens were collected to validate the imact of IGFBP-7 on the efficacy of EGFR TKI treatment . Results: IGFBP-7 is over-expressed in gefitinib-resistant cells. The IGFBP-7 mRNA expression in the malignant pleural effusion of patients with acquired resistance to EGFR TKI was significant higher than that in the treatment-naïve patients. Knockdown IGFBP-7 reverses gefitinib resistance in PC9/gef cells. Knockdown IGFBP-7 could increase gefetinib induced-apoptosis through the regulation of BIM. IGFBP-7 affected the mechanism of EGFR TKI resistance resulted from inhibition of IGF-IR.. In clinical practice, low IGFBP-7 serum level is associated with longer progression free survival (PFS) of EGFR TKI as the first line treatment. Furthermore, lower IGFBP-7 level of resected tumor predicts a longer 5-year tumor relapse-free survival. Positive IGFBP-7 immunoihistochemical stain could predict a shorter PFS of the first-line EGFR TKI treatment. Conclusions: IGFBP-7 confers resistance to the EGFR TKI and may be a target for future treatment investigation." @default.
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- W2892018778 date "2017-05-20" @default.
- W2892018778 modified "2023-10-17" @default.
- W2892018778 title "IGFBP-7 to confer resistance to the epidermal growth factor receptor tyrosine kinase inhibitor." @default.
- W2892018778 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.e20572" @default.
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