Exosome-mediated organotropism in breast cancer metastasis: bridging the gap between molecular mechanisms and clinical application.

Breast cancer (BC) is characterised by multiple metastasis to various organs and remains a leading contributor to the approximately 10 million annual cancer-related deaths worldwide. The choice of organ for a metastatic site is not random and follows the principle of organotropism. This review develops the concept that exosomes-small extracellular vesicles 30-150 nm in diameter-play a substantial role in forming the pre-metastatic niche by selectively reprogramming target cells and tissues, thereby preparing the organ for the arrival of tumour cells. We examine in detail the molecular mechanisms whereby exosome-contained microRNAs, annexins, tetraspanins and other components drive osteolysis of bone tissue, increase the permeability of the blood-brain barrier (brain metastases arise in roughly 25-27% of triple-negative and 11-20% of HER2-positive BC), and induce fibro-inflammatory changes in the lungs and liver. Particular attention is given to the translational potential of exosomes as diagnostic markers-recent exosome-based classifiers reach a diagnostic accuracy of about 90%-and as agents of targeted therapy. Through a structured comparison of more than twenty primary studies, we provide a critical analysis of the methodological heterogeneity of exosome research and of the status of current clinical trials (8 of 13 catalogued BC trials are purely observational). On this basis, the review outlines concrete, source-supported ways to overcome the existing barriers on the path "from the bench to the bedside".