In the article, the authors note that the peptide is produced in large quantities by some malignant tumors. Their work clarifies its mechanism of action: The peptide inhibits endothelial cell migration and angiogenesis by activating protein kinase A. Protein kinases are regulatory proteins that are responsible for processes such as cell proliferation and migration.

"We've identified a key kinase that, when activated, causes endothelial cells to commit suicide," said the paper's senior author Judith Varner, Ph.D. "But it only causes suicide in endothelial cells that are activated by tumors and other disease states. This mechanism doesn't become activated in normal blood vessels."

Understanding the underlying mechanism is important, Varner says, because it provides a way in which future research may lead to the development of new drug or gene therapies. In the current paper, the researchers tested various methods of local delivery and enzyme activation by drug or gene therapy to inhibit angiogenesis.

"We can activate protein kinase A with a common drug called cyclic AMP, and we can also activate it through gene therapy," she said. "We are vigorously pursuing a gene therapy approach and possibly a drug therapy here [at the University of California at San Diego]."

The next step will be to develop a chemically synthesized particle or agent that will deliver the gene or drug only into proliferating endothelial cells. To do this, the researchers must target a receptor expressed only on proliferating endothelial cells and not in large quantities on normal, existing endothelial cells. To that end, Varner and colleagues are working to develop a bioconjugate, also called a micro-particle.

"It may sound strange to be working with radiologists on gene therapy," Varner said. "But the same kinds of particles or bioconjugates used for imaging can be used to deliver a gene. You create a micro-particle, attach to it a molecule that will bind to a receptor on the target cell, and use it to deliver DNA directly into that cell. This is an emerging technology in gene therapy and in imaging."

In other work, Varner is collaborating with the same radiology team to develop a cancer-imaging agent designed to find and highlight tiny new tumors and allow clinicians to visualize metastases.