X-Message-Number: 9951 Date: Sun, 28 Jun 1998 09:36:27 -0700 (PDT) From: Doug Skrecky <> Subject: are angiostatin and endostatin cures for cancer? Commentary from The Lancet 351: 1598-1599 May 30,1998 By Adrian Harris, Imperial Cancer Research Fund, Univerisity of Oxford Quote from text: "In experiments, administration of angiostatin inhibited growth of primary tumours and metastases. Inhibition of metastases was by a novel mechanism, prevention of blood-vessel formation, so the tumour cells grew at the same rate but died much more rapidly by apoptosis, because of lack of oxygen and nutrients. Endostatin caused nearly complete regression of established tumours, but tumours regrew when therapy was stopped. However, surprisingly after several rounds of therapy, residual cells did not regrow but remained dormant. This effect occurred also in tumours extremely resistant to chemotherapy. Thus, despite residual cells, endostatin was highly effective, and its combination with angiostatin may be even more so. These data have not been published, and a few weeks ago an optimistic newspaper report based on these findings stimulated a flurry of publicity and changes in share prices. Are angiostatin and endostatin the cure for cancer? There are many problems to be solved. Initially scale-up of the production of proteins is necessary, and in the studies with endostatin "unrefolded" protein had to be used. Recombinant angiostatin has been made on a small scale, and recent publication of the crystal structure of endostatin may help in the development of smaller molecules and peptides with activity. The receptors or targets are unknown and may not be expressed on human tumour vessels or to the same extent as in murine vessels. The animal tumours were very small compared with the tumours in patients eligible for phase I trials. The human pharmacokinetics may make the proteins difficult to deliver, and if receptors or mechanisms were known, more appropriate drugs may be developed. Thus these proteins are far from being ready for clinical use." Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=9951