CANCER METASTASIS - A SEARCH FOR THERAPEUTIC INHIBITION

Failure of cancer treatment is often due to the growth of secondary me tastatic lesions in distant organs. Because initiation of metastasis i s an entry event in malignancy patients often present not only with a primary tumor but also with occult metastases. Treatment of these meta stases requires aggressive, systemic chemotherapy, since surgical remo val of all metastatic foci is normally not feasible. However, drug tox icity caused by many of the currently used anticancer agents often lim its chemotherapeutic approaches to malignant disease. In contrast, the development and use of novel cytostatic, antimetastatic agents could be less toxic and more applicable for long-term treatment in combating latent and/or residual disease. Practical intervention with such nont oxic agents has been envisioned as maintenance therapy after cytoreduc tion of a tumor or as a prophylactic treatment after the removal of a precancerous tumor exhibiting a genetic predisposition to a carcinomat ous state. In this review, we discuss targets of the metastatic cell t hat may be potentially exploitable with chemotherapy, and present the current status of several novel, antimetastatic agents. Clinical evalu ation of such agents will require new and appropriate clinical models for evaluating their antimetastatic efficacy. The recent successes ach ieved with certain proteinase inhibitors for the treatment of cancer a re paving the way for the development of other therapeutic agents of t his type, aimed at unique biochemical pathways associated with oncogen ic behavior.