What is the most promising strategy for the treatment of metastasizing melanoma?

The treatment of patients with metastasizing melanoma, still one of the mos t deadly diseases in modern medicine, ranks among the greatest challenges t hat a clinician has to face. Metastatic melanoma also is one of the most pr ofound sources of clinical frustration, since it provides far more ultimate ly defeating experiences than clinical victories. At the same time, the fas cinating biology of melanoma has invited the study of this neuroectodermal tumor as a model system for dissecting many of the key problems of modern o ncology, ranging from molecular oncogenesis via the controls of tumor proli feration, apoptosis, invasion, metastasis, and angiogenesis to tumor immuno surveillance and tumor drug resistance. Together,vith the dire need to deve lop more effective treatment modalities for improving both life expectancy and quality of life of affected patients, this has made metastatic melanoma a favorite model for the exploration of innovative strategies for tumor ma nagement. Encouragingly, many of these have already generated very promisin g results in animal models. However, this impressive level of research prog ress in conquering melanoma in the animal room contrasts rather pitifully w ith the actual progress made on the ward. This CONTROVERSIES feature, there fore, critically and soberly reviews the state of the art of treating metas tatic melanoma today (distinguishing between nodal and distant metastases), and sharply defines unresolved or comparatively neglected key problems. In addition, this feature highlights several novel, provocative, hitherto und erappreciated, yet potentially promising treatment approaches that deserve systematic exploration. Hopefully, this will offer further inspiration for the design and pursuit of innovative anti-melanoma strategies off-the-beate n-track.