Figure 1.

Key targets of the metastatic cascade. Metastatic tumor cells form cytoprotective complexes with host platelets or with each other, while traveling to secondary sites (bone) via the vascular system (Survival in the circulation). Circulating tumor cells arrest in blood vessel constrictions, and transmigrate through the endothelial layer with the assistance of platelets (Extravasation). Within the bone, tumor cells enter a pre-arranged cytoprotective niche assembled with the aid of local stromal cells and matrix bound/soluble factors. Tumor cells may remain dormant or establish proliferative secondary lesions (Secondary lesion formation). Each metastatic step has a unique set of targetable determinants, which are displayed as step specific “heat maps”.