Protein-protein interactions as therapeutic targets in breast cancer: integrated computational and experimental advances, mechanisms and clinical translation.

Breast cancer is a highly heterogeneous malignant tumour, whose initiation and progression are closely associated with aberrant rewiring of protein-protein interactions (PPIs). This review systematically summarizes the core regulatory mechanisms of PPIs in breast cancer: focusing on neomorphic interactions (neoPPIs) and hypomorphic interactions (hypoPPIs) induced by driver mutations, and dissecting their regulatory effects on key pathways such as apoptotic pathways, DNA damage repair, and hormone receptor signalling. It also summarizes the application progress of critical technologies for PPI research in breast cancer. Furthermore, the review highlights the clinical translational value of PPIs as diagnostic biomarkers and therapeutic targets, along with the development and clinical exploration of targeted strategies such as BCL-2 inhibitors and molecular glues. Finally, it discusses the current challenges in breast cancer PPI research, including heterogeneity and drug resistance mechanisms, and prospects future directions such as single-cell level dynamic analysis and artificial intelligence (AI)-assisted drug design. This review provides a new theoretical basis and technical support for the precision treatment of breast cancer.