For several years, cancer researchers have tried to develop therapies that work not by directly killing tumor cells, but by depriving them of the blood supply they need to live and grow. New results, published in the number of Science , 16 May should spur the field. The work suggests that tumor response to radiotherapy depend on the fact that the radiation kills the small blood vessels that feed the tumor. The finding may pave the way for better therapies for the treatment of cancers resistant to irradiation.
Researchers had thought that the radiation kills tumor cells directly. But 2 years ago, a team led by biologist Richard Kolesnick cancer and Zvi Fuks radiologist at Memorial Sloan Kettering Cancer Center, New York has shown that one of the main side effects of radiotherapy, damage to the gastrointestinal tract, occurs because the radiation induces apoptosis, a form of cell suicide, in the cells of small blood vessels, channels. They have also linked this to production apoptosis induced by radiation from a chemical called ceramide. They found that mice that do not make ceramide because they lack an enzyme called acid sphingomyelinase (asmase) are protected against damage. Fuks Kolesnick and then decided to see if the cells of the blood vessels of cancerous tumors are also vulnerable to radiation.
The current work shows that they are. transplanted tumors, for example, grow faster in mice in which the gene was knocked asmase than in normal mice. Tumors growth in engineered mice are also much more resistant to radiation, apparently because the cells of their blood vessels, unlike those tumors in normal mice, undergo little apoptosis in response to radiotherapy.
Cancer Center researcher Robert College Health Sciences Kerbel of the Sunnybrook and Women in Toronto researchers described the work as "elegant. using knockout strain of mice, they showed very conclusive proof of concept "that therapies that target tumor blood vessels can improve tumor responses to treatment. Kerbel also noted that the results link with the work of his group and others showing that something similar happens with cancer chemotherapy.
Fuks suggests that the results could improve radiotherapy. He stresses that cancers might be able to resist radiation because they dump factors that stimulate the growth of blood vessels, thus counteracting the apoptosis induced by radiation. It may be possible to improve the apoptosis of blood vessel cells, or with drugs that block the activity of factors or stimulating asmase activity.
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