Therapeutic targets for antimetastatic therapy.

Metastases are responsible for most cancer deaths. Despite dramatic advances in cancer therapy, the presence of metastases implies a significantly shortened survival and reduced quality of remaining life. Aside from prevention of cancer altogether, or significant improvements in early detection for most cancers, effective novel therapeutic strategies targeting metastasis should provide the greatest clinical benefit. Metastasis research has shown that many of the initial steps in metastasis are completed with a high degree of efficiency and may have occurred by the time of clinical diagnosis. Therefore, targeting the later stages of metastasis may offer a more promising therapeutic approach for the development of antimetastatic therapies. Appropriate clinical strategies include targeting dormant solitary cells, active preangiogenic metastases, or vascularised metastases. Dormancy of solitary single cells, seen clinically and experimentally, may be an explanation for cancer recurrence. Eradication or inactivation of these dormant cells could provide large benefit for patients. However, little is known about what makes cancer cells dormant and, therefore, a greater knowledge of the mechanisms of dormancy is needed. This review discusses potential biological targets, as defined by the steps in the metastatic process, for antimetastatic therapies and provides examples of clinical strategies for preventing or treating successful metastasis.