Ionizing radiation is a widely used treatment for solid tumors; local tumor control by radiotherapy usually requires the complete sterilization of all tumor clonogens (stem cells). It is also possible that the microvasculature, rather than the clonogenic component, could be the primary target for radiation, but the evidence to support this hypothesis has been sparse. In the May 16 Science, Monica Garcia-Barros and colleagues at the Memorial Sloan-Kettering Cancer Center show that tumor response to radiotherapy is regulated by vascular endothelial cell apoptosis (Science, 300:1155-1159, May 16, 2003).

Garcia-Barros et al. grew MCA/129 fibrosarcomas and B16F1 melanomas in apoptosis-resistant acid sphingomyelinase (asmase)–deficient, or Bax-deficient, mice. They observed that these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, were resistant to single-dose radiation up to 20 grays (Gy).

"Our data define microvascular damage as a key mechanism in tumor response to radiation at...

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