Editorial [Hot topic: Target Therapy of Bone Metastases and Tumours (Guest Editors: M. Caraglia and D. Santini)]

We hope that you will find the reviews in this special issue of Current Cancer Drug Targets informative and stimulating so that together we can contribute to found new strategies for treatment of cancer and its effects. Cancer metastasis is a complex cascade of events that includes detachment of metastatic cells from the primary tumour and invasion of the surrounding interstitial stroma, entry of the metastatic cells into the circulatory system (intravasation), arrest in distant organs via interactions of tumour cells with platelets, macrophages and the vascular and lymphatic endothelium, and exit from the bloodstream (extravasation) which thereby gain tumour cells access to the surrounding parenchyma of the target organ where they thrive to form secondary tumours. The cells comprising the premetastatic niche express integrins, which provide a permissive environment for the migrating tumor cells. In addition, various growth factors and cytokines in the bone marrow such as endothelin, transforming growth factor (TGF)-β, IL-6, and IL-8 serve as paracrine regulators of the initial growth of metastatic tumor cells. The interaction of receptor molecules in the bone marrow stroma with the integrins that are over-expressed on the tumor cells promotes colonization of circulating malignant cells in the bone marrow. As described by P. Clezardin, αvβ3 integrin facilitates the colonization of bone by osteotropic cancer cells. Moreover, osteoclasts (the bone-resorbing cells) also express αvβ3 integrin. Bone desease is the hall-mark clinical feature of several cancers, as multiple myleoma, sarcoma, prostate, lung and breast cancer.