By David N. Leff
In addition to his comments on University of Chicago oncologist Ralph Weichselbaum's studies in today's Nature, researcher Michael O'Reilly provided an update of his work with surgeon Judah Folkman at Harvard University-affiliated Children's Hospital.
Folkman and O'Reilly, in the Nov. 27, 1997, Nature reported discovering two angiogenesis inhibitors, angiostatin and endostatin, that have become the focus of evaluation as anticancer agents by numerous laboratories.
"We're in the process of finishing up the studies for the manuscript that's going to follow up the paper in Nature last November," O'Reilly told BioWorld Today. "In it we reported we were able to treat the tumors repeatedly with endostatin, up and down, and put them into microscopic dormancy.
"We think that the models we have of self-sustained dormancy," he continued, "may help us better understand why some cancer patients will have dormant disease for so long, and then all of a sudden the cancer starts growing again.
"The obvious implication," he pointed out, "is that if you know what triggers that relapse, you could intervene before it happens. So our next paper is going to be how those models of dormancy are regulated. Hopefully, we'll have that submitted to Nature within a month."
As to whether dormancy occurs in combined endostatin-angiostatin therapy or only in each separately, O'Reilly said, "The study we did to address that was very small, in only four mice. We found that not only do they have an additive effect, but they synergize. The effect of the combination is greater than either one alone.
"In those four mice," he continued, "there's a chance that we may have actually eradicated the tumor cell. So right now we're doing the more definitive studies."
O'Reilly continued, "We've just started doing three different tumors in large numbers of mice, comparing high doses of either one alone to lower doses of the combination. Those studies, unfortunately for me, really take a long time. Because in order to establish that the tumors aren't going to come back, you have to treat them down to dormancy, then wait several months.
"But those studies are under way," he concluded, "and hopefully by the end of this year, we'll have them out." *