Fig. 9: mTORC1 inhibition in PanNETs. | npj Systems Biology and Applications

Fig. 9: mTORC1 inhibition in PanNETs.

From: A systems biology approach to define mechanisms, phenotypes, and drivers in PanNETs with a personalized perspective

Fig. 9

mTORC1 knockout and its combination with mTORC2 knockout was simulated and evaluated in both WT and MEN1 loss conditions (a). Based on the in-silico results a resistant phenotype could be observed after single mTORC1 inhibition or together with mTORC2. The cascade from the severe cancer phenotype to the mTORC1 resistant phenotype was studied to infer its mechanistic behavior (b). Here, genes are listed on the side. mTORC1 is highlighted in red to indicate it was targeted via knockout in the cascade. Node activities are depicted via colored boxes. Green indicates active while gray indicates inactive nodes. A summary of the hypothesized mechanism of mTORC1 resistance is represented in an interaction graph (c). Here mTORC1 is highlighted in red. Activities of nodes directly downstream of mTORC1 are depicted with red arrows pointing upwards (activated during resistance) or downwards (inhibited during resistance). The color of the nodes reflects the activities in the attractor cascade.

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