Decoding resistance mechanisms and synergistic interventions in Breast Cancer: an integrative analysis of PI3K-Hippo-MAPK signalling crosstalk

Therapeutic resistance remains a major challenge facing breast cancer, and growing evidence has demonstrated that intricate interplays among cancer-inducing pathways enable tumour cells to evade the effects of cancer therapy. This thesis goes beyond studying pathways in isolation by employing an integrative systems biology approach, empowered by mechanistic network modelling, to systemically characterise the dynamic PI3K-Hippo-MAPK crosstalk in breast cancer. Our integrative systems biology study uncovers hidden adaptive resistance mechanisms and establishes a mechanistic model of the signalling crosstalk, which serves as a powerful framework for devising novel, effective combination therapies in breast cancer.