Metastasis: a therapeutic target for cancer

Metastasis remains the major driver of mortality in patients with cancer. The similarities and differences between primary tumors and metastases are described, and pathways controlling the colonization of a distant organ and incorporation of anti-metastatic therapies into clinical testing are discussed. The authors emphasize that the time is ripe for metastasis and metastatic colonization to enter mainstream clinical development and testing. Metastasis remains the major driver of mortality in patients with cancer. Our growing body of knowledge regarding this process provides the basis for the development of molecularly targeted therapeutics aimed at the tumor cell or its interaction with the host microenvironment. Here we discuss the similarity and differences between primary tumors and metastases, pathways controlling the colonization of a distant organ, and incorporation of antimetastatic therapies into clinical testing. Key Points Most information on human cancer is obtained from analysis of primary tumors and yet this knowledge is applied to the treatment of metastases There is mounting genetic evidence that the molecular wiring of a metastatic lesion has both elements in common with and elements that are distinct from those of primary tumors Targeting the last step in the metastatic process, outgrowth at a distant site, termed 'metastatic colonization', holds great therapeutic promise Blockade of metastatic colonization can be accomplished by targeting the metastatic cancer cell or the host cell, or by interrupting reciprocal interactions between tumor cells and the foreign microenvironment; therapeutic efforts can target metastatic colonization at all sites or interactions specific to a particular organ (bone, for instance) Novel clinical trial designs with short-term molecular and pharmacodynamic end points should be considered Approaches to inhibit metastatic colonization may show their best efficacy in the adjuvant setting