173P - Vascular endothelial growth factor-C promotes EGFR-TKIs resistance and cancer stemness via SLUG of non-small cell lung cancer

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Ching-Chia Cheng
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors C. Cheng1, J. Su2
  • 1Graduate Institute Of Life Sciences, National Defense Medical Center, 114 - Taipei/TW
  • 2National Institute Of Cancer Research, National Health Research Institutes, Miaoli County/TW



Acquired resistance to the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, is a critical issue of lung cancer therapy. Vascular endothelial growth factor C (VEGF-C) promote lymphangiognesis and cancer progression but the detailed mechanism related to EGFR-TKIs resistance and cancer stemness remain mostly unclear.


The expression levels of VEGF-C and SLUG in lung cancer patients with gefitinib responder (n = 41) and gefitinib non-responder (n = 39) were examined by quantitative RT-PCR and Oncomine database analysis. The effect of VEGF-C and SLUG on EGFR-TKIs resistance by MTT assay and cancer-stem-like properties by quantitative RT-PCR in vitro.


In this study, we observed that high level of VEGF-C correlated to EGFR mutation-independent gefitinib resistance and cancer-stem-like properties in vitro and in vivo; lung cancer patients with high VEGF-C expression had high level of cancer stem cell markers and worst progression-free survival. Moreover, we found a transcription factor, SLUG, involved in VEGF-C/VEGFR3-induced gefitinib resistance and cancer stemness of lung cancer.


These results suggest that VEGF-C is a critical role for EGFR-TKIs resistance and cancer stemness of lung cancer, and targeting VEGF-C/VEGFR3/SLUG pathway may provide a potential therapeutic strategy for lung cancer patient with acquired resistance to EGFR-TKIs.

Clinical trial identification

Legal entity responsible for the study

Jen-Liang Su


Ministry of Science and Technology, Taipei, Taiwan


All authors have declared no conflicts of interest.