Prospects for inhibiting angiogenesis

A recent paper (Cell1997;88:277–85) has shown that a novel angiogenesis inhibitor TNP 470 has the ability to induce tumour growth regression without causing drug resistance. Anticancer therapy is plagued with problems of drug resistance, which relate to the ease with which the tumour cell genome can change expression. An alternative approach is to target the tumour blood supply since the endothelial cells should have a more stable genome. In preliminary studies TNP470, a synthetic inhibitor of angiogenesis, was found not to induce drug resistance on repeated use as tumours regressed and recurred. Now, the same group of researchers has reported on a similar lack of drug resistance to a natural angiogenesis inhibitor, endostatin, which is a 20 000 Da C terminal fragment of collagen type XVIII produced by haemangioendothelioma. Endostatin specifically inhibits proliferating endothelial cells but has no effect on resting endothelial cells. In addition, all treated tumours regressed to microscopic size and, with cycling endostatin therapy, no macroscopic or microscopic tumours were found. Remarkably, all tumours eventually became dormant even when the endostatin treatment was stopped. The potential value for ophthalmic use is immediately obvious, particularly if endostatin can be administered locally and repeatedly without loss of potency. Apart from its obvious use in the treatment of intraocular malignancy, both topical and intraocular application might have wide use in conditions such as proliferative diabetic retinopathy, …