Genetic Finding Could Lead to Cancer Therapy
In a discovery that could point the way toward new cancer therapies, Johns Hopkins scientists have uncovered information about the genetics of tiny blood vessels that nourish tumors and enable them to spread.
The scientists, reporting in today’s edition of Science, say they have isolated 46 genes that are mysteriously “turned on” in tumor vessels but are inactive in the vessels that flow through normal tissue.
Such genes could become new targets for cancer researchers who, in the last several years, have become intrigued with the idea of shrinking tumors by starving them of their blood supply.
The leading proponent of this theory, Dr. Judah Folkman of Harvard University, said he considered the paper a “landmark.”
“You read it and put it down, but you know that labs are suddenly going to be working on this all over the world,” said Folkman, who has a laboratory at Boston’s Children’s Hospital.
The finding is being reported by a scientific team at the Johns Hopkins Oncology Center that has made fundamental discoveries about the role that genes play in triggering cancer, particularly colon cancer. Its work has focused largely on the malignant cells and the precancerous growths that give rise to them.
But now, the team--led by Drs. Kenneth Kinzler and Bert Vogelstein--has turned its attention to the tumor’s blood supply.
Without it, tumors cannot grow larger than a pea. To expand, the tumor recruits a blood supply from surrounding tissues. Capillaries that are only a cell wide grow into the tumor, forming a shapeless tangle.
“They don’t have a nice straight path,” said Dr. Brad St. Croix, lead author in the paper appearing in Science. “They are tangled, and go all over the place. The flow is often erratic and often static as it gets scrunched by the tumor.”
The finding could be used to find new treatments aimed at starving tumors. One strategy would be to fashion new drugs--or find old ones already on the shelf--that are capable of switching off the genes that trigger the vessels’ growth.
Another would be to kill the vessels by delivering toxins to proteins that are made by the active genes and lie on the cell surface. To get the toxins to their target, scientists could attach them to antibodies that are programmed to seek out the proteins.
This would be the pharmaceutical equivalent of a smart weapon, a vehicle that seeks and destroys offending tissues while leaving others intact. One of the big problems of anti-cancer drugs is that they harm healthy tissues along with cancerous ones, producing wrenching side effects.
St. Croix said the finding provides a foundation for new treatments, but in no way represents a treatment breakthrough.
“I don’t want to oversell it,” he said. “It’s still a very basic study. It’s got lots of potential, but we’re still in the early stage.”
Folkman said the discovery could have implications for diseases other than cancer that depend on the abnormal growth of blood vessels. These include macular degeneration, psoriasis, rheumatoid arthritis and endometriosis, a common gynecological disease.
