Melanogenesis and melanoma

Abstract

Melanins are the principal surface pigments in vertebrates and, in humans, play a major role in photoprotection. Although the product (melanin) has a mainly protective function in the skin, the process of melanogenesis represents a potential cellular hazard and is confined to special membrane-limited organelles (melanosomes) in a set of specialized dendritic cells (melanocytes) which synthesize the pigment and transfer it to recipient cells. Malignant melanocytes tend to exhibit up-regulated melanogenesis and defective melanosomes. These features suggest ways in which anti-melanoma therapy may be specifically targeted. Two general chemotherapeutic modalities are considered: 1 The 'Achilles heel' approach in which the generation of reactive quinones capable of leaking into the cytosolic compartment and causing structural and functional derangement is encouraged by the use of analogue substrates. 2 The 'Trojan horse' approach, in which a cytotoxic agent is selectively released by a tyrosinase-dependent mechanism.