Folkman Optimistic About Angiogenesis Research
"As cancer treatments become more targeted and less toxic, how much earlier can we treat cancer and what difference will it make?"
Speaking October 5 at the NCI CCR grand rounds, Dr. Judah Folkman, Andrus Professor of Pediatric Surgery at Children's Hospital in Boston and professor of cell biology at Harvard Medical School, used this question to frame his talk on whether the "angiogenic switch" - in which tumors gain the ability to recruit a blood supply and grow - can be prevented.
"There's an enormous amount of data that says when you are diagnosed with cancer, it has been on the way for many years," he said. Given that reality, he asked, are clinicians and the research community missing an opportunity by using angiogenesis inhibitors in the same way clinicians use other treatment modalities - only after patients have symptoms, the tumor is located, and has started to cause damage? The available genetic and clinical evidence on angiogenesis inhibitors, Dr. Folkman argued, suggests that they could be used to prevent tumors from ever forming or to keep small, harmless tumors in check.
In a study published in Cancer Cell last year, for instance, researchers showed that if just one angiogenesis inhibitor, tumstatin, was knocked out in wild-type mice, tumor growth increased by 400 percent. However, adding back physiologic levels of tumstatin returned the tumor to its baseline growth rate; increasing those levels shrunk tumors even further. Dr. Folkman also pointed to research on patients with Down syndrome who, with the exception of testicular cancer, almost uniformly fail to get solid tumors. A study in the European Journal of Human Genetics in 2001 appears to explain why. In the study, researchers found that, compared with normal controls, people with Down syndrome had twice the levels of the angiogenesis inhibitor endostatin, a cleavage product of collagen VIII whose gene is present on chromosome 21. (Down syndrome patients have an extra copy of chromosome 21.)
To date, Dr. Folkman noted, his lab has identified three angiogenesis-based biomarkers. Using imaging techniques that take advantage of luciferase, the lab has been able to view tumors down to 100 microns and actually measure when a tumor jumps to an angiogenic phenotype. "For the first time now," he said, "we can see the angiogenic switch, measured by light flux, 3 weeks before you can palpate a 50-millimeter tumor."