| Trials of multiple therapies have recently validated angiogenesis as a target in oncology. The effective inhibition of angiogenesis is likely to require a multi-targeted approach. However, inhibiting angiogenesis might promote metastasis, therefore new anti-angiogenic therapies might need to concurrently control metastasis. A multi-target and novel antiangiogenic/antimetastatic approach, combined with a good safety and tolerability profile, is a key differentiator between PI-88 and other antiangiogenic investigational drugs based on the evidence to date. It may well provide a competitive advantage over targeted agents that rely on only a single mode of action. The major issues for the treatment of cancer remain: the need to attack the growth of the primary (original) tumour, to inhibit the establishment and spread of secondary tumours (metastasis). PI-88 has been demonstrated to address both of these issues simultaneously, by utilising the mechanism of heparan sulfate mimicry. PI-88 retards the growth of primary tumours by inhibiting new blood vessel growth (angiogenesis) in three ways. The first is heparan sulfate mimicry, which causes inhibition of heparanase, and prevents the release of angiogenic growth factors from the extracellular matrix (ECM). The second is the interaction with angiogenic growth factors VEGF (Vascular Endothelial Growth Factor), FGF-1 (Fibroblast Growth Factor -1) and FGF-2, which reduces their functional activity, as PI-88 binds with high (nanomolar) affinity to these growth factors. Thirdly, PI-99 stimulates the release of Tissue Factor Pathway Inhibitor (TFPI), an endogenous protein that has anti-angiogenic and anti-coagulation properties. Inhibition of heparanase and stimulation of TFPI release are also jointly responsible for the antimetastatic activity of PI-88. | |
