Interfering with hemostatic system components: possible new approaches to antiangiogenic therapy

Inhibition of angiogenesis has progressed from a theoretical and esoteric discipline scrutinized in but a few laboratories far removed from the clinic, to mainstream experimental clinical cancer therapeutics. Dramatic progress in this field represents a triumph of the concept of translational biomedical research. Growth of knowledge in this discipline has brought to light a bewildering yet tantalizing array of interacting enzymatic algorithms that participate in the highly orchestrated process of new blood vessel formation critical for tumor growth and dissemination. It is clear that pathways of blood coagulation (in broad context) and angiogenesis are inextricably linked. The facts that much is already known about many components of these pathways and that stalling of tumor growth has already been demonstrated for several interventions aimed at participants in these reactions send a clear signal that more effective and less toxic cancer therapy may be at hand in the near future. There is no lack of candidate targets for intervention brought to light by preclinical scientists. Numerous well-characterized investigational agents are on hand for testing. The challenge is clearly in the hands of the clinical investigators to proceed with human intervention studies while armed with knowledge of opportunities and pitfalls that should guide insightful clinical trial design. A particularly compelling feature of this treatment paradigm is that it is not aimed directly at destruction of tumor through inhibition of the DNA replication machinery of the cell. Rather it is aimed at restoring the normal state by modulating the dysregulated interaction of tumor cells with their environment that is characteristic of cancer.