Induction of Cisplatin Resistance by Hormones in Breast Cancer

Cisplatin is an effective anti-cancer drug which has been successfully utilized in the treatment of many cancer types. However, cisplatin has shown only limited efficacy in the majority of breast tumors, and is not generally included as a monotherapy in this disease. The potential role of hormones in chemoresistance in breast cancer has received little attention. This review focuses on two classes of hormones: a) protein hormones that include prolactin, growth hormone and leptin, all of which act via class 1 cytokine receptors and activate the Jak2/stat signaling pathway, and b) steroid hormones that include estrogens, xenoestrogens, and glucocorticoids, which generally act via ligand-regulated nuclear receptors. Accumulating evidence indicate that each of these hormone antagonizes cisplatin cytotoxicity in breast cancer cells by a variety of mechanisms. The implications of chemoresistance by these hormones to patients with hormone-sensitive breast cancer, and the potential benefits of increasing chemosensitivity by using anti-hormone treatment regimens are discussed.