Spatiotemporal dynamics of the pre-metastatic niche: remodeling of lung microenvironment before breast cancer metastasis and targeted intervention strategies

Breast cancer lung metastasis has attracted considerable research attention because of its complex molecular heterogeneity and refractory characteristics. Development of the pre-metastatic niche (PMN) is a key initiating event in the cancer metastatic cascade. The PMN can remodel the tissue microenvironment through the spatiotemporal induction of extracellular matrix remodeling, activation of inflammatory responses, formation of an immunosuppressive state, vascular anomalies, and metabolic reprogramming. In this review, we present a novel framework for the dynamic evolution of PMN in breast cancer, focusing on the mechanisms of cell-molecule network synergy during PMN formation in the lungs of patients with breast cancer. Additionally, we systematically review novel PMN monitoring modalities and therapeutic strategies targeting key regulatory nodes, and discuss the bottlenecks and potential solutions for their clinical translation. We aim to provide a scientific foundation for the development of preventive and therapeutic strategies for breast cancer lung metastasis based on the molecular characteristics of PMN and to provide a theoretical basis for breast cancer lung metastasis research and drug development.