Milea Timbergen

36 and HES1 in DTF cells by Western Blot analysis. Additionally, it was demonstrated that PF-03084014, decreased NICD and HES1 expression in a dose dependent manner in DTF cells, and that Notch signalling inhibition contributed to impaired DTF cell proliferation by inducing a cell cycle G1 arrest and decreasing migration and invasion (Table 1) 62 . Two other clinical trials (a phase 1 trial with seven DTF patients and phase 2 trial with seventeen DTF patients) showed promising results with a significant part of patients experiencing partial response or stable disease (Table 2) 77, 78 . Figure 3 displays the Notch pathway and putative drug targets in the context of DTF. Figure 3. A schematic presentation of the Notch signalling pathway and the drugs that interfere with this pathway in DTF. The graph depicts that the Notch signalling pathway can be targeted by the use of γ-secre- tase inhibitors e.g., PF-03084014. 2

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