Estrogen receptors as the novel therapeutic biomarker in non-small cell lung cancer

Figure 1 Intracellular estrogen receptor and epidermal growth factor receptor signaling pathway in non-small cell lung cancer. A: Mechanisms of ER and EGFR signaling in NSCLC. E2 (17β-estradiol)-bound ER acts in part as a transcription factor in the nucleus. Once the ER binds to the DNA in the estrogen response element of a gene, it generally recruits co-activator complexes to modulate gene transcription (genomic signal). In addition, E2-bound ER also acts in the cytoplasm (non-genomic signal) by interacting with downstream mediators of EGFR signaling, such as MAPK and PI3K/AKT. EGFR is a cell membrane receptor tyrosine kinase that transmits a signal when it binds EGF; B: Mechanisms of combination therapy for NSCLC. The estrogen antagonist fulv binds to ERs and blocks estrogen signaling. EGFR-TKIs, such as gefitinib or erlotinib, bind to mtEGFR and inhibit EGFR signaling. Both treatments block the interaction between ER and EGFR signaling. EGFR: Epidermal growth factor receptor; ER: Estrogen receptor; TKI: Tyrosine kinase inhibitor.