from a pointer, today's BioCentury article "Pharmacogenetics might have helped"............
Science 2002 Feb 22;295(5559):1526-8
Effect of p53 status on tumor response to antiangiogenic therapy.
Yu JL, Rak JW, Coomber BL, Hicklin DJ, Kerbel RS.
Sunnybrook and Women's College Health Sciences Centre, Molecular and Cellular Biology Research, Room S-218, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.
The p53 tumor suppressor gene is inactivated in the majority of human cancers. Tumor cells deficient in p53 display a diminished rate of apoptosis under hypoxic conditions, a circumstance that might reduce their reliance on vascular supply, and hence their responsiveness to antiangiogenic therapy. Here, we report that mice bearing tumors derived from p53(-/-) HCT116 human colorectal cancer cells were less responsive to antiangiogenic combination therapy than mice bearing isogenic p53(+/+) tumors. Thus, although antiangiogenic therapy targets genetically stable endothelial cells in the tumor vasculature, genetic alterations that decrease the vascular dependence of tumor cells can influence the therapeutic response of tumors to this therapy. |
