PIK3CA and neoplasm: Interestingly, a number of research in recent years have discovered that the estrogen receptor ERB works as a mitogen in NSCLC cells, and that the bidirectional signaling loop between the estrogen and EGFR pathways increases tumor-associated angiogenesis while accelerating NSCLC growth, furthermore, let-7c is significantly up-regulated in anti-estrogenic (fulvestrant)-treated cells, and let-7c increases gefitinib sensitivity via RAS inhibition, PI3K/AKT inactivation, and the mitogen-activated extracellular signal-regulated kinase (MEK)/ERK signaling pathway (76).