CELL-CYCLE ARREST VERSUS CELL-DEATH IN CANCER-THERAPY

In response to anticancer therapeutics, human colon cancer cells growi ng in vitro either enter into a stable arrest or die, depending on the integrity of their cell-cycle checkpoints(1). To test whether altered checkpoints can modulate sensitivity to treatment in vivo, xenografts were established from isogenic lines differing only in their p21 chec kpoint status. Although all tumors with intact checkpoint function und erwent regrowth after treatment with gamma-radiation, a significant fr action of checkpoint-deficient tumors were completely cured. This diff erence in sensitivity was not detected by the clonogenic survival assa y, because both arrest and death preclude outgrowth of colonies. These results demonstrate that checkpoint status affects sensitivity to ant icancer treatments in vivo, and these findings have important implicat ions for identifying and testing new therapeutic compounds.