%0 Journal Article %1 Meier2007 %A Meier, F. %A Busch, S. %A Lasithiotakis, K. %A Kulms, D. %A Garbe, C. %A Maczey, E. %A Herlyn, M. %A Schittek, B. %D 2007 %J British Journal of Dermatology %K 2007 izi kulms %N 6 %P 1204--1213 %R 10.1111/j.1365-2133.2007.07821.x %T Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment %U https://www.ncbi.nlm.nih.gov/pubmed/17388918 %V 156 %X Background  In melanoma, several signalling pathways are constitutively activated. Among them, the RAS/RAF/MEK/ERK (MAPK) and PI3K/AKT (AKT) signalling pathways are activated through multiple mechanisms and appear to play a major role in melanoma development and progression. Objectives  In this study, we examined whether targeting the MAPK and/or AKT signalling pathways would have therapeutic effects against melanoma. Methods  Using a panel of pharmacological inhibitors (BAY 43-9006, PD98059, U0126, wortmannin, LY294002) we inhibited the MAPK and AKT signalling pathways at different levels and evaluated the effects on growth, survival and invasion of melanoma cells in monolayer and organotypic skin culture. Results  Antiproliferative and proapoptotic effects of inhibitors alone in monolayer culture were disappointing and varied among the different cell lines. In contrast, combined targeting of the MAPK and AKT signalling pathways significantly inhibited growth and enhanced apoptosis in monolayer culture. To verify our data in a more physiological context we incorporated melanoma cells into regenerated human skin mimicking the microenvironment of human melanoma. Combinations of MAPK and AKT inhibitors completely suppressed invasive tumour growth of melanoma cells in regenerated human skin. Conclusions  Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment and should encourage further in-depth investigations. %Z Meier, FBusch, SLasithiotakis, KKulms, DGarbe, CMaczey, EHerlyn, MSchittek, BengResearch Support, Non-U.S. Gov'tEnglandBr J Dermatol. 2007 Jun;156(6):1204-13. doi: 10.1111/j.1365-2133.2007.07821.x. Epub 2007 Mar 28. %7 2007/03/29 %@ 0007-0963 (Print) 0007-0963 (Linking)

@article{Meier2007, abstract = {Background  In melanoma, several signalling pathways are constitutively activated. Among them, the RAS/RAF/MEK/ERK (MAPK) and PI3K/AKT (AKT) signalling pathways are activated through multiple mechanisms and appear to play a major role in melanoma development and progression. Objectives  In this study, we examined whether targeting the MAPK and/or AKT signalling pathways would have therapeutic effects against melanoma. Methods  Using a panel of pharmacological inhibitors (BAY 43-9006, PD98059, U0126, wortmannin, LY294002) we inhibited the MAPK and AKT signalling pathways at different levels and evaluated the effects on growth, survival and invasion of melanoma cells in monolayer and organotypic skin culture. Results  Antiproliferative and proapoptotic effects of inhibitors alone in monolayer culture were disappointing and varied among the different cell lines. In contrast, combined targeting of the MAPK and AKT signalling pathways significantly inhibited growth and enhanced apoptosis in monolayer culture. To verify our data in a more physiological context we incorporated melanoma cells into regenerated human skin mimicking the microenvironment of human melanoma. Combinations of MAPK and AKT inhibitors completely suppressed invasive tumour growth of melanoma cells in regenerated human skin. Conclusions  Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment and should encourage further in-depth investigations.}, added-at = {2018-02-01T15:51:58.000+0100}, annote = {Meier, FBusch, SLasithiotakis, KKulms, DGarbe, CMaczey, EHerlyn, MSchittek, BengResearch Support, Non-U.S. Gov'tEnglandBr J Dermatol. 2007 Jun;156(6):1204-13. doi: 10.1111/j.1365-2133.2007.07821.x. Epub 2007 Mar 28.}, author = {Meier, F. and Busch, S. and Lasithiotakis, K. and Kulms, D. and Garbe, C. and Maczey, E. and Herlyn, M. and Schittek, B.}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2aaea3bf6a426a593b5b98f4fc7564ae4/cristiano}, doi = {10.1111/j.1365-2133.2007.07821.x}, edition = {2007/03/29}, interhash = {ac76f7a79f9bd9668a249c64b4885a7f}, intrahash = {aaea3bf6a426a593b5b98f4fc7564ae4}, isbn = {0007-0963 (Print) 0007-0963 (Linking)}, issn = {00070963}, journal = {British Journal of Dermatology}, keywords = {2007 izi kulms}, number = 6, pages = {1204--1213}, pmid = {17388918}, timestamp = {2018-07-25T12:32:22.000+0200}, title = {{Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment}}, url = {https://www.ncbi.nlm.nih.gov/pubmed/17388918}, volume = 156, year = 2007 }