PARIS--Worldwide, some 50 clinical trials involving up to 1,000
patients are now attempting to define the clinical utility of
angiogenesis inhibitors in reining in micrometastases. The rationale
for such "dormancy therapy" lies in a hypothesis formulated
by Judah Folkman, MD, of Harvard.
If tumor size is ultimately controlled by endothelial proliferation,
a primary tumor might suppress the growth of distant metastases
by delivering an endothelial inhibitor to the metastases through
the circulation. This hypothesis could account for the explosive
growth of metastases observed in some patients after excision
of the primary tumor.
In his acceptance of the Claude Jacquillat Award at the Sixth
International Congress on Anti-Cancer Treatment (ICACT), Dr. Folkman
described the laboratory studies of tumor angio-genesis that have
since given rise to a new perspective in oncology.
Initially, Dr. Michael O'Reilly, working in Dr. Folkman's laboratory,
observed in an animal model that removal of a primary Lewis lung
tumor led to the rapid growth of metastases.
Dr. O'Reilly and his colleagues further found that the primary
tumor produced a specific endothelial inhibitor that circulated
for 2½ days.
This 38-kd protein, now known as angiostatin, proved capable of
inhibiting capillary and aortic endothelial cells while having
no effect on carcinoma cells, fibroblasts, or smooth muscle cells.
"Most human tumors are angiogenic," Dr. Folkman said,
"but some release an inhibitor of endothelial growth that
can go to a remote site and some don't."