CURRENT AND FUTURE STRATEGIES TO BLOCK TUMOR ANGIOGENESIS, INVASION, AND METASTASIS

Progression of malignancy involves a series of sequential steps that u ltimately lead to cancer-cell dissemination. In addition to the loss o f growth control, an imbalanced regulation of motility and proteolysis is a prerequi-site for invasion and metastasis. These factors are als o necessary for angiogenesis - an integral process occurring at both t he primary and the metastatic sites. Investigators have elucidated in detail many of the molecular mechanisms involved in the sequential ste ps of the metastatic cascade and have thereby provided new targets for therapeutic intervention. For each step, different model systems have been developed and various strategies for antimetastatic therapy have been tested in vitro as well as in murine systems. Difficulties in tr anslating results obtained in preclinical models into the clinical set ting have become apparent and have not been unexpected in light of the sometimes highly artificial interaction in the experimental setting. Nevertheless, continued development of model systems and further resea rch into the genetic control of malignancy should lead to the identifi cation of common signal-transduction pathways. Interference at such si tes promises to be particularly effective in inhibiting proliferation and metastasis.