Targeting bone metastases starting from the preneoplastic niche: home sweet home

Philippe Clezardin in his original and complete review masterfully describes the bone metastasis process [1]. It seems to share many analogies with a famous fairy tale:'Once upon a time a very poor woodcutter lived in a tiny cottage in the forest with his two children, Hansel and Gretel. His second wife often ill-treated the children and was forever nagging the woodcutter. "There is not enough food in the house for us all. There are too many mouths to feed! We must get rid of the two brats," she declared' [2].The determinants of 'successful' metastatic growth in a given organ (for example, bone marrow) are not completely understood, but there is a clear evidence to suggest that tumor cells and host tissue both play important roles in the metastatic process. This model is based on experimental data evaluating cancer stem-like cells, a population of cells within a tumor mass able to leave the primary tumor mass and navigate through the blood-stream to localize in new sites where the 'soil' can exert an important role on their fate [3,4]. For this reason, pre-metastatic niches are thought to be fertile regions of tissue that facilitate the invasion, survival and/or proliferation of metastatic tumor cells, providing a highly novel mechanism for the promotion of metastasis [5]. Moreover, chemokines are small chemo-attractant cytokines that bind to specific G-protein-coupled transmembrane receptors present on the plasma membranes of target cells. These molecules can guide circulating cancer cells to the bone. So we can postulate that cross-talk between the bone microenvironment and cancer cells can facilitate bone tropism of cancers cells.'On [Hansel and Gretel] walked and walked, till suddenly they came upon a strange cottage in the middle of a glade. "This is chocolate!" gasped Hansel as he broke a lump of plaster from the wall. "And this is icing!" exclaimed Gretel, putting another piece of wall in her mouth. Starving but delighted, the children began to eat pieces of