Angioprevention with fenretinide: targeting angiogenesis in prevention and therapeutic strategies

Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR; fenretinide), a synthetic retinoic acid derivative, is a highly active and promising therapeutic and chemopreventive agent. Fenretinide shows biological activity against numerous cancer types in vitro and in preclinical studies. Clinical trials have shown that fenretinide induces a significant reduction of second breast cancer in premenopausal women. Several studies on different neoplasms are ongoing, such as breast and ovarian cancer, neuroblastoma, glioblastoma, head and neck and skin cancers and others. It has minimal side effects in humans, so that trials in young women at high-risk of breast cancer and ovarian and for the prevention of other tumor types such as lung cancer could be envisaged. Here we review some ongoing clinical trials and evaluate the possible mechanisms underlying the secondary chemopreventive effects of 4HPR. In particular we report basic and translational data on the anti-angiogenic “angiopreventive” properties of fenretinide, its anti-invasive activity, its ability to induce apoptosis and to generate or enhance production of reactive oxygen species as possible molecular bases for a chemopreventive action in patients.