Differential effects of cell cycle regulatory protein p21WAF1/Cip1 on apoptosis and sensitivity to cancer chemotherapy

p21 (WAF1/Cip1) was initially identified as a cell cycle regulatory protein that can cause cell cycle arrest. It is induced by both p53-dependent and p53-independent mechanisms. This mini-review briefly discusses its currently known functions in apoptosis and drug sensitivity. As an inhibitor of cell proliferation, p21 (WAF1/Cip1) plays an important role in drug-induced tumor suppression. Nevertheless, a number of recent studies have shown that p21 (WAF1/Cip1) can assume both pro- or anti-apoptotic functions in response to anti-tumor agents depending on cell type and cellular context. This dual role of p21 (WAF1/Cip1) in cancer cells complicates using p21 (WAF1/Cip1) status to predict response to anti-tumor agents. However, it is possible to develop p21 (WAF1/Cip1) -targeted reagents or p21 (WAF1/Cip1) gene transfer techniques to have a beneficial effect within a well-defined therapeutic context. Better understanding of the roles of p21 (WAF1/Cip1) in tumors should enable a more rational approach to anti-tumor drug design and therapy. (C) 2003 Elsevier Ltd. All rights reserved.