Radiation does not kill cells that line the intestinal tract by damaging their genetic material, says a report in the July 13 issue of Science by a team at Memorial Sloan-Kettering Cancer Center in New York City. Instead, the radiation damages the tiny blood vessels that feed the cells, which die as their blood supply is cut off.
The finding could limit the damage of radiation therapy and affect cancer treatment in other ways, the researchers say.Among other things, the finding supports the controversial angiogenesis theory of Dr. Judah Folkman of Harvard Medical School, which says cancers can be treated by attacking the blood vessels on which they rely. Folkman, co-author of an editorial accompanying the published report, says the finding "could have profound implications for cancer therapy."
The finding is based on "what some people call the new biology," says research leader Richard N. Kolesnick, head of the Memorial Sloan-Kettering Signal Transduction Laboratory. Instead of working with cells grown in culture, the effects of radiation were studied in animal tissues, which "are an order of magnitude greater in complexity," he says.
The study, which used epithelial tissue, the lining of the gastrointestinal tract, of mice, showed the radiation damage "was probably not due directly to the epithelial components but rather to the microcirculation, the loss of blood flow at the smallest level of blood vessels, the capillaries," Kolesnick says.
While the tissue was not cancerous, "at least this model suggests that in some instances, the primary target of radiation therapy is the blood supply," says Dr. Zvi Fuks, a radiation oncologist at Memorial Sloan-Kettering and a member of the research team.
"The target is better defined, and we can think of a variety of ways to improve therapy," says Fuks.
"There are two possibilities," says Kolesnick. "We could protect normal tissue better, or we could deprotect the tumor. Either way would create a better therapeutic ratio, with less damage to normal tissue."
The researchers say one way to protect normal tissue is to inject a protein, called basic fibroblast growth factor, to prevent the death of the cells lining the gastrointestinal tract. But, they say the protection is limited, since the growth factor does not prevent the destruction of bone marrow cells.
Fuks says what's important is that the work provides "proof in principle that tissue damage can occur through damage to blood vessels. Here we can provide genetic and pharmacological information about normal tissue, and, conceptually, it is related to cancerous tissue."
The next step is to study the effect of radiation on tumor microvasculature, the smallest vessels that supply the blood on which a cancer relies, Kolesnick says. "There is a great potential for this concept in terms of applications for what we do with patients with cancer," but a lot of work is needed to fulfill the potential, he says.
What To Do: The research may not produce an immediate payoff, but the potential is there. For information about radiation therapy and other cancer treatments, go to the National Cancer Institute or the American Cancer Society.