The Critical Role of PPAR gamma in Human Malignant Melanoma

The past 30 years have only seen slight improvement in melanoma therapy. Despite a wide variety of therapeutic options, current survival for patients with metastatic disease is only 6-8 months. Part of the reason for this treatment failure is the broad chemoresistance of melanoma, which is due to an altered survival capacity and an inactivation of apoptotic pathways. Several targetable pathways, responsible for this survival/apoptosis resistance in melanoma, have been described and current research has focused on mechanism inactivating these pathways. As PPAR gamma was shown to be constitutively active in several tumour entities and PPAR gamma agonists extent strong anticancer effects, the role of PPAR gamma as a possible target for specific anticancer strategy was investigated in numerous studies. However, only a few studies have focused on the effects of PPAR gamma agonists in melanoma, showing conflicting results. The use of PPAR gamma agonists in melanoma therapy has to be carefully weighted against considerable, undesirable side effects, as their mode of action is not fully understood and even pro-proliferative effects have been described. In the current review, we discuss the role of PPARs, in particular PPAR gamma in melanoma and their potential role as a molecular target for melanoma therapy. Copyright (c) 2008 Christian Freudlsperger et al.