The Critical Role of PPARgamma 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 PPARgamma was shown to be constitutively active in several tumour entities and PPARgamma agonists extent strong anticancer effects, the role of PPARgamma as a possible target for specific anticancer strategy was investigated in numerous studies. However, only a few studies have focused on the effects of PPARgamma agonists in melanoma, showing conflicting results. The use of PPARgamma 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 PPARgamma in melanoma and their potential role as a molecular target for melanoma therapy.
Freudlsperger
Christian
C
Department of Oral and Maxillofacial Plastic Surgery, Tübingen University Hospital, Osianderstrasse 2-8, 72076 Tübingen, Germany.
Schumacher
Udo
U
Reinert
Siegmar
S
Hoffmann
Jürgen
J