Therapy of metastatic malignant melanoma: on the way to individualized disease control.

After decades of therapeutic frustration, the identification of some fundamental molecular drivers finally set the stage for the development of targeted therapies of metastatic malignant melanoma. With the invention of B-RAF inhibitors, targeting the mutated and activated B-RAF molecule in the MAP kinase cascade, objective responses can be achieved in about 50% of those cases harbouring this specific mutation. However, the effects are often short-lived with an average duration of 5-6 months. Hence, the challenge is to make such remissions stable and prevent secondary resistance. Currently, both the combination of targeted drugs and the invention of effective immunomodulating antibodies, e.g., anti-CTLA4 as well as anti-PD1, hold great promise to proceed on the way to individualized disease control, if not, as a remote aim, cure of this deadly cancer. Finally, progress has been made in identification and targeting of cancer stem cells, which seem to exhibit a kind of primary drug resistance and create the source of relapses and growth of clones with acquired secondary drug resistance.