P21 Waf1/Cip1 as a therapeutic target in breast and other cancers

The cyclin kinase inhibitor p21, originally described as a universal inhibitor of cyclin-dependent kinases, has since been shown to have additional functions other than CDK inhibition. It is likely that a key role of p21 is to keep cells alive after DNA damage and subsequent p53 induction, in order for the cell to effect repairs. Thus, the increase in p21 seen in some cancers may impart these cells with a survival advantage. Here we discuss how this antiapoptotic aspect of p21 makes it an attractive target for cancer therapy; attenuation of p21 in malignant cells may subvert the normal repair process induced by DNA-damaging chemotherapeutic agents and thus make such drugs more effective.