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Humboldt-Universitaet zu Berlin - Collaborative Research Center for Theoretical Biology

Modelling of signalling cascades – the impact of the RAS pathway on transcriptional targets

Recently, the RAS pathway hit the headlines of translational cancer research again due to the finding that KRAS mutations have an impact on the clinical response toward receptor-targeted cancer therapies. Mutational activation of KRAS is primarily associated with therapy resistance, while wild-type KRAS activity is associated with a therapeutic benefit, however, only in a subset of cancer patients. At present, therapy responders and non-responders cannot be distinguished in molecular terms that would enable knowledge-based treatment allocation. Therefore, signalling processes downstream of the RAS molecular switch are among the prime candidate mechanisms to be screened for clinically relevant alterations. Particularly, studying stimulus-response characteristics, dynamics and feedback regulation of the RAS/MAPK pathway and of other RAS-dependent pathways as well as assessing the integration of pathway activation with the transcriptional program are of utmost importance for defining functionally relevant nodes for therapeutic intervention and for identifying prognostic parameters.

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