Medical management of advanced melanoma

Despite major advances in the treatment of many solid tumours, metastatic melanoma remains stubbornly resistant to therapeutic attack with systemic agents. Much of the resistance of melanoma to immunotherapy and cytotoxic treatment is due to an impressive array of molecular defences that derive ultimately from the essential molecular structure of the melanocyte and its biological requirement for defence against apoptosis. Patients with metastatic disease should be cared for by a multidisciplinary team with a coordinating clinical nurse consultant playing a central role. In selected patients observation remains the best initial management. All eligible patients should be entered on clinical trials of new treatments. Standard systemic therapy consists of chemotherapy with dacarbazine, but response rates are less than 10% in recent Phase III trials. The Ras-RAF signalling pathways are commonly constitutively activated in melanoma and newly tested inhibitors of these, like sorefenib, may sensitise melanoma cells to cytotoxic attack. Considerable hope is also provided by recent Phase II trials with immunotoxins. These provide novel opportunities for targeted therapy in the treatment of melanoma.