Metastases are resistant to multiple therapies and are responsible for the large majority of cancer-related deaths. However, the molecular and cellular mechanisms driving metastasis formation remain to be elucidated and better described in a realistic in vivo context. Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the contribution of biomechanics is poorly known. In addition, tumor extracellular vesicles have been shown to shape premetastatic niches and thereby favor metastastic colonization, but detailed information and mechanisms are missing. Moreover, new approaches need to be designed to specifically target and impair tumor progression. In the past years, we have: 1. Developed a pioneer and unique intravital CLEM (Correlative Light and Electron Microscopy) technology that is perfectly suited for tackling key biological events driving tumor invasion and metastasis formation. 2. Identified new molecular players in the biogenesis and function of tumor exosomes. 3. identified the contribution of hemodynamic forces to tumor cell extravasation preceding metastasis formation.