The transcription factor hypoxia-inducible factor-1α (HIF-1α), whose levels are substantially elevated in several tumour types, represents a major molecular target for the development of new anti-cancer drugs. The synthetic non-steroidal estrogen diethylstilbestrol (DES) blocks HIF-dependent hypoxic responses, and its administration at low doses prior to chemotherapy represents a promising option to improve the treatment of castration-resistant prostate cancer. However, DES use is limited by poor water solubility and wide-ranging dose-related toxicities.
