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Zhenxiang Li



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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.51 - ERβ1 Expression Patterns have Different Effects on EGFR TKIs Treatment Response in EGFR Mutant Lung Adenocarcinoma. (ID 2913)

      00:00 - 00:00  |  Presenting Author(s): Zhenxiang Li

      • Abstract
      • Slides

      Introduction

      Estrogen receptor β can lead to rapid activation of signaling through nongenomic mechanism which may associate with EGFR TKIs treatment response. However, the mechanism still needs to be verified.

      Methods

      Lentivirus expression vectors containing ERβ1 and ERβ5 expression element were used for establishment of EGFR mutant lung adenocarcinoma cell lines highly expressing ERβ1 and both ERβ1 and ERβ5- named as PC9/ ERβ1 and PC9/ERβ1/5. Relative mRNA expression level of ERβ1 and ERβ5 was measured using SYBR green assay. Immunocytochemistry and immunofluorescence were used to determine the ERβ1 localization within the cells. Immunoblotting analysis was used to detect the expression level of proteins involved in related signal pathways. Cell viability test and cell colony assay were conducted to test the sensitivity of gefitinib treatment for the cells. The patients with EGFR mutant advanced lung adenocarcinoma were enrolled in this retrospective study for ERβ1 and survival analysis. Statistical tests were conducted to analyze the difference using Graphpad 8.0.

      Results

      We constructed a stable lung adenocarcinoma cell lines with EGFR 19 exon deletion mutation expressing higher level of ERβ1 and both ERβ1/ERβ5 respectively named as PC9/ ERβ1 and PC9/ ERβ1/5 (A). Immunofluorescence showed that ERβ1 located mainly within nucleus in PC9/ ERβ1 whereas a relatively high nuclear and cytoplasmic ERβ1 was detected in PC9/ ERβ1/5 (B). Western blot showed that the downstream signaling of EGFR was still higher activated in PC9/ ERβ1/5 compared to that of PC9 and PC9/ERβ1 except mTOR signal pathway under treatment of gefitinib and estradiol simultaneously (C). CCK8 and cell colony assay showed that gefitinib sensitivity was downregulated for PC9/ERβ1/5 compared to that for PC9/NC and PC9/ERβ1 through anti-apoptosis (D-F). The ERβ1 expression was found in nuclear, both nuclear/cytoplasm and cytoplasm respectively (G). There is no significant difference of PFS between the patients with ERβ1 positive and those with ERβ1 negative (H). We next combined patients with n/cERβ1 expression and the ones with cERβ1 into one group, named as cytoERβ1. Cases with cytoERβ1 expression had a shorter median PFS compared to patients with nERβ1 expression (I).

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      Conclusion

      Our study showed that ERβ1 localized in the cell cytoplasm through interaction with ERβ5, subsequently induced non-genomic signaling activation, mediating EGFR TKIs resistance in EGFR mutant lung adenocarcinoma. The result indicated that anti-estrogen therapy might reverse EGFR TKIs treatment resistance to some extent in selected patients.

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      P76.54 - Prognostic Value of Radiotherapy Pattern for Late-Stage Epidermal Growth Factor Receptor (EGFR) Mutant Lung Adenocarcinomas (ID 3068)

      00:00 - 00:00  |  Presenting Author(s): Zhenxiang Li

      • Abstract
      • Slides

      Introduction

      There is still no study to assess the value of radiotherapy pattern on prognosis for late-stage EGFR mutant non-small cell lung cancer. The aim of the study is to investigate the role of different pattern of local radiotherapy in the management of stage IV epidermal growth factor receptor (EGFR) mutated non-small cell lung cancers (NSCLCs) treated with EGFR tyrosine kinase inhibitors (TKIs).

      Methods

      Patients with stage IV EGFR mutant NSCLCs treated with radiotherapy concomitant to EGFR TKIs treatment were retrospectively identified. Overall survival (OS) were analyzed as endpoints of the study. Kaplan-Meier method was used in survival analysis, and logarithmic rank test was used to compare the effects of individual variables on different results (P < 0.05 was considered to be statistically significant).

      Results

      figure.jpg

      A total of 205 patients were enrolled in the study from May 2010 to December 2017. 111 patients received one-time single site radiotherapy (SSR) and 94 patients received multiple sites radiotherapy (MSR). Those who received MSR had longer OS (median 40.0 months; 95% CI, 29.6 to 50.4) than those who received SSR (median 28.9 months; 95% CI, 24.3 to 33.5; P=0.031). We further analyzed the impact of different organs or sites irradiation on OS. The median OS of patients who had received thoracic radiotherapy and those who had not received thoracic radiotherapy was 41.7 months (95% CI, 29.0 to 54.4) and 27.1 months (95% CI, 22.7 to 31.5), respectively (log-rank P0.001) (Figure).

      Conclusion

      Multiple sites radiotherapy improved survival outcomes in late-stage lung adenocarcinoma patients with EGFR-sensitive mutations; further, thoracic radiotherapy played the most important role in improving prognosis.

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