It has been shown that insulin-like growth factor 2 (IGF-2) and insulin growth factor receptor 1 (IGF-1R) were significantly reduced in human colon cancer cells (HT-29) treated with luteolin, thereby inhibiting the activation of the IGF-1R signaling pathway and ultimately further inhibiting the PI3K/AKT pathway from exerting anti-tumor effects.[46] It is noteworthy that the IGF signaling pathway can synergize with estrogen receptor (ER)-positive tumors to proliferate and metastasize,[47] and many breast cancers are stimulated to progress by IGF-1. The gene discussed is ESR1; the disease is breast carcinoma.