Knowing that iPS cells tend to induce tumors known as teratomas when inserted into mice, Ryeom guessed that teratomas grown from iPS cells with an extra chromosome 21 would have far fewer blood vessels than teratomas from iPS cells with the normal number of chromosomes. She was right: blood vessels budded in the Down teratomas, but never fully formed.

"The studies in the iPS cells helped validate and confirm that the suppression of angiogenesis that we saw in mouse models also holds true in humans," says Ryeom. "It suggests that these two genes might point to a viable cancer therapy."

Ryeom's group has identified which part of the DSCR1 protein blocks calcineurin and is testing to see whether that fragment can be delivered specifically to endothelial cells, to prevent them from forming new blood vessels, without affecting calcineurin pathways in other cells and causing side effects. "Immunosuppressive drugs also target calcineurin in T-cells," Ryeom notes. "We think that Dscr1 blocks calcineurin specifically in endothelial cells, without affecting T-cells, but we need to check."

Folkman's interest in why patients with Down syndrome have such a reduced risk for cancer focused on endostatin, an anti-angiogenic compound made by the body. Discovered in the Folkman lab, endostatin is a fragment of collagen 18 -- whose gene is also on chromosome 21. People with Down syndrome reportedly have almost doubled levels of endostatin because of the extra copy of the gene.

"I think there may be four or five genes on chromosome 21 that are necessary for angiogenesis suppression," says Ryeom. "In huge databases of cancer patients with solid tumors, there are very few with Down syndrome. This suggests that protection from chromosome 21 genes is pretty complete."

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