Resistance to antiangiogenic cancer therapy

Angiogenesis inhibitors are potent anticancer drugs thought to lack acquired drug resistance problems because they target the normal endothelial cells of the tumor vasculature. But, in February 22 Science, Joanne Yu and colleagues from University of Toronto, Canada, show that p53 loss in tumor cells confers a resistance to hypoxia that might reduce the efficacy of antiangiogenic therapy.

Yu et al. compared the response to antiangiogenetic therapy of tumors derived from paired isogenic p53^-/- and p53+/+ HCT116 human colorectal carcinoma cells. They found that mice bearing tumors derived from p53^-/- HCT116 cells were less responsive to antiangiogenic combination therapy than mice bearing isogenic p53+/+ tumors (Science 2002, 295:1526-1528).

The authors concluded that, "it is essential to consider the possibility that the vascular dependence of tumor cell populations may be heterogeneous, variable, and quantitative, rather than absolute and qualitative in nature. These considerations not...