Mechanisms of action of topical 5-fluorouracil: Review and implications for the treatment of dermatological disorders

Topical 5-fluorouracil has proved to be a useful therapy since its discovery nearly 50 years ago for the treatment of a range of cancers (e.g. skin, colorectal, breast) and dermatological conditions (e.g. cancerous and precancerous conditions such as actinic keratosis, benign tumors, nail psoriasis, mycosis fungoides, and porokeratoses). As a result of the enduring utility in these conditions, the mechanism of action of 5-fluorouracil has been studied extensively in vivo and in vitro. This review provides an overview of the history and general mechanism of action of 5-fluorouracil and discusses the dermatological implications of the drug, including systemic absorption, selectivity for abnormal skin, targeted delivery, and skin-specific molecular effects. Considerations of 5-fluorouracil treatment in specific dermatological settings are also discussed, as well as recent findings of a role for 5-fluorouracil in the treatment of photoaging.