Two Steps Forward . . .

Abstract

Most conventional cancer drugs gradually lose their effectiveness because tumor cells are genetically unstable and can readily acquire mutations that confer drug resistance. It had been hoped that drug resistance would not be a problem for angiogenesis inhibitors because these drugs target endothelial cells in the tumor vasculature, which are genetically stable. However, Yu et al. found that mice bearing human colorectal tumors deficient in the tumor suppressor protein p53 were less responsive to antiangiogenic therapy than those bearing tumors with normal p53 function. The most likely explanation is that p53 loss confers an improved capacity to grow in low-oxygen conditions on the tumor cells. Because p53 is mutated in most human cancers, these results could have important implications for the design and interpretation of clinical trials testing antiangiogenic drugs. J. L. Yu, J. W. Rak, B. L. Coomber, D. J. Hicklin, R. S. Kerbel, Effect of p53 status on tumor response to antiangiogenic therapy. Science 295, 1526-1528 (2002). [Abstract] [Full Text]