APE1 promotes EGFR-TKI acquired resistance in non-small cell lung cancer through regulating epithelial to mesenchymal transition

Cancer Diagnostics Conference & Expo

June 13-15, 2016 Rome, Italy

Xiao Yang and Mengxia Li

Daping Hospital, China

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

While EGFR-tyrosine kinase inhibitors (TKIs) significantly improve the survival and quality of life in advanced non-small cell lung cancer (NSCLC) patients carrying EGFR mutations, its acquired resistance limits the clinical benefit thus becoming a big concern of oncologists� community. The current study reported that human apurinic/apyrimidinic endonuclease 1 (APE1) plays pivotal roles in EGFR-TKI resistance and the expression of APE1 in the biopsy tissue pretreatment could be a predictive marker for the survival of EGFR-TKI treatment. This implies a possible predicting strategy for EGFR-TKI responses by detecting tissue, or monitoring serum APE1 levels. More importantly, the APE1 redox inhibitor, E3330, turned back on cellular response to EGFR-TKIs in established resistant cell lines further suggests a promising therapeutic combination of APE1 inhibitor and EGFR-TKIs with hope of continuous clinical benefit. To link APE1 to the responses to EGFR-TKIs in NSCLC, the protein level of APE1 were analyzed in cancerous tissue of NSCLC patients receiving EGFR-TKIs treatment. The correlation between APE1 expression and progression-free survival (PFS), overall survival (OS) or response rate were analyzed. The impact on EGFR-TKI responses by APE1 was measured by exogenously manipulation of APE1 in EGFR-TKI sensitive and resistant cell lines. Further mechanistic studies were performed to explore the regulatory roles of APE1 in important EGFR-TKI resistance related process, epithelial-to-mesenchymal transition (EMT) by detection of E-cadherin and vimentin markers. The current study revealed a significant role of APE1 in EGFR-TKI resistance via a novel regulatory effect on EMT in NSCLC. It suggested the potential of APE1 inhibitors in combination of EGFR-TKIs for continuous clinical benefit in NSCLC patients carrying EGFR mutations.

Biography :

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