The RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways present molecular targets for the effective treatment of advanced melanoma.
Malignant melanoma is a highly aggressive tumor of the pigment-producing cells in the skin with a rapidly increasing incidence and a poor prognosis for patients with advanced disease that is resistant to current therapeutic concepts. Therefore, the development of novel strategies for treating melanoma are of utmost importance. In melanoma, both the Ras-Raf-MEK-ERK (MAPK) and the PI3K-AKT (AKT) signaling pathways are constitutively activated through multiple mechanisms, and thus exert several key functions in melanoma development and progression. Conversely, several molecules known to play key roles in melanoma development and progression such as the adhesion molecules E-/N-cadherin, MelCAM and alphavbeta3 integrin are regulated by these pathways and/or activate the same. The results of the research to date indicate that in melanoma both the MAPK and the AKT signaling pathways may represent promising therapeutic targets.
Meier
Friedegund
F
Department of Dermatology, University of Tuebingen, Tuebingen, Germany. friedegund.meier@med.uni-tuebingen.de
Schittek
Birgit
B
Busch
Silke
S
Garbe
Claus
C
Smalley
Keiran
K
Satyamoorthy
Kapaettu
K
Li
Gang
G
Herlyn
Meenhard
M
D017209:Apoptosis; D049109:Cell Proliferation; D058534:Class I Phosphatidylinositol 3-Kinases; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000503:physiopathology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D020928:Mitogen-Activated Protein Kinases