From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Sun Jun 28 1998 - 10:35:49 MDT
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."
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