PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
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cell lines tested, suggesting that the PI3K/AKT pathway is more important for cell<br />
survival in NRAS mutant melanoma cells. However, targeting of PI3K and mTORC1/2<br />
with new dual inhibitors in combination with MEK1/2 inhibitors is necessary to<br />
effectively abolish the growth of NRAS melanoma cells in vitro and in vivo. Furthermore,<br />
we showed that MEK and PI3K/mTOR1/2 inhibition acts synergistically. Kinome analysis<br />
confirms that the combination of MEK and PI3K/mTOR inhibition predominantly affects<br />
genes in the RAS pathway and growth factor receptor (GFR) pathways, which signal<br />
through MEK and PI3K/mTOR, respectively. Synergy is supported by the fact that more<br />
genes are affected by the combination treatment compared to single inhibitor use. The<br />
preclinical data presented in this work shows that combined MEK/ERK and PI3K/mTOR<br />
pathway inhibition has antitumor activity and might serve as a therapeutic option in<br />
the treatment of NRAS mutant melanoma, for which there are currently few effective<br />
therapies.<br />
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