Fenretinide and its relation to cancer

Retinoids, natural or synthetic substances which have vitamin A activity, have a well-known reputation for their antitumour and differention-inducing activity in vitro and in vivo. More than 1500 retinoids have been tested so far but very few of them have been entered into clinical trials because of their side-effects. All-trans-N-(4-hydroxyphenyl)retinamide (4HPR or fenretinide) is a synthetic retinoid that is reported to have fewer side-effects compared to naturally occurring retinoids such as all-trans retinoic acid (ATRA) and 9-cis retinoic acid. In addition, fenretinide has been shown to induce cell death (apoptosis) even in ATRA-resistant cell lines. Although the mechanism by which fenretinide acts is not entirely known it is considered to be a promising drug and seems to induce apoptosis via different pathway(s) from classical retinoids. In this reveiw, we discuss possible mechanisms of fenretinide action and summarize results of clinical trials.