Between 1970 and 1994, cancer claimed the lives of about 0.5 million Americans every year. According to the most recent statistics, it is estimated that approximately 1.3 million new cases of cancer will be diagnosed and 555,500 people will die from cancer in the United States in the year 2002. Despite these statistics, the prognosis of some cancers is excellent. Melanoma offers one good example. If diagnosis is made before the cancer has spread from its site of original, cure is commonly achieved. As with most cancers however, melanomas that have spread to distant organs are rarely cureable. The development of therapeutic strategies for the prevention and treatment of metastatic cancers thus represents a key priority for the pharmaceutical industry. Metastasis is a multi-step process that involves the attachment of cancer cells to blood vessels supplying distant organs. Cell attachment occurs under flow conditions and recent data emerging from the Scripps Research Institute suggests that this involves tumor cell interaction with attached, activated platelets. This is mediated by tumor cell integrin alphavbeta3 (vitronectin) and crosslinking plasma protein ligands. To analyze the mechanism of tumor cell ligand interactions under dynamic flow conditions, this group of researchers used real-time video microscopy and tested human melanoma cell binding to fibrinogen, von Willebrand Factor or fibronectin matrices. When perfused at venous flow, melanoma cells arrested abruptly and began to spread immediately. This was uniquely mediated by integrin alphavbeta3, and required the activation of this integrin and actin polymerization. LeadDiscovery is currently producing a DiscoveryDossier overviewing the role that cells and molecules of the coagulation system play in the development of cancer, and how this could be exploited by the pharmaceutical industry. This recent data provides yet another example of the interaction of these systems and suggests that blocking the binding of tumor cells to activated platelets by targeting integrin alphavbeta3 could offer hope in the treatment of metastasis. This integrin has already received considerable attention as a target for arthritis and cancer, and antagonists have been developed in order to prevent angiogenesis (see also "Focus on Metastasis" section of this edition of TherapeuticAdvances), however the ability of this class of molecule to prevent metastatic cell adhesion represents a newer field.

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