Decoding the adaptive survival mechanisms of breast cancer dormancy
Francis M. Barnieh, Jamie Morton, Olaitan Olanrewaju, Sherif F. El‐Khamisy
Abstract
Breast cancer (BC) recurrence remains a major clinical challenge, leaving patients in perpetual uncertainty about disease relapse after primary treatment. BC dormancy, an adaptive survival state of disseminated tumour cells, is a key driver of both early and late recurrence. However, the mechanisms regulating BC dormancy remain poorly understood. Emerging evidence suggests that tumour hypoxia, extracellular matrix (ECM) remodelling, and therapy-induced stress drive dormancy by altering cellular metabolism, gene expression, and immune interactions, enabling long-term survival of dormant BC cells. With no dormancy-specific therapies currently approved, a deeper understanding of dormancy-associated survival mechanisms is crucial for identifying therapeutic targets and developing strategies to eradicate dormant BC cells, thereby preventing recurrence and improving patient outcomes. This review comprehensively examines major dormancy-inducing factors and the adaptive survival mechanisms of dormant BC cells. We also highlight critical gaps in preclinical models that hinder the translation of preclinical cancer dormancy insights into clinical applications and propose potential therapeutic strategies to prevent BC recurrence.