Taken together, we suggest a positive feedback mechanism between PI3K/Akt signaling and ATF5, where PI3K/Akt activation by insulin or IGF-I promotes ATF5 expression in breast cancer cells, and ATF5 further promotes the activation of PI3K/Akt pathway, thereby emphasizing the importance of targeting ATF5 in anticancer therapy, particularly, in diabetic patients with breast cancer. The gene discussed is ATF5; the disease is breast cancer.