Systematic analysis of network-driven adaptive resistance to CDK4/6 and oestrogen receptor inhibition using meta-dynamic network modelling.

Heterogeneity in protein signalling networks, especially reaction coefficients, drives adaptive resistance to CDK4/6 and oestrogen receptor inhibitors, as shown by MDN modelling.

• Why it matters: Understanding how molecular heterogeneity influences adaptive resistance is crucial for improving targeted cancer therapies and preventing disease relapse.
• What they did: Using a novel Meta Dynamic Network (MDN) modelling approach, the study analyzed how heterogeneity affects early cell cycle regulation and resistance mechanisms in cancer cells, focusing on reaction coefficients and protein abundance.
• The result: The findings reveal reaction coefficients as key drivers of resistance, enabling the prediction of resistance pathways and supporting the development of more effective, network-informed treatment strategies.