Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs

Author(s): L. A. Stivala, O. Cazzalini, E. Prosperi.

Abstract:

p21CDKN1A (WAF1/CIP1/SDI1), the cyclin-dependent kinase (CDK) inhibitor belonging to the Cip/Kip family, was first described as a potent inhibitor of cell proliferation and DNA replication, both in physiological conditions and after DNA damage. More recently, p21 has been recognized to play additional and fundamental roles in other important pathways, including regulation of transcription, apoptosis and DNA repair. Knock-out mouse studies combined with biochemical and functional analysis of cells in culture have indicated a tumor suppressor activity for p21. However, these lines of evidence have been complicated by other findings indicating that p21 can exhibit oncogenic properties. In fact, the evidence that p21 expression may lead to proliferation arrest, is counterbalanced by the rescue of tumor cells from drug-induced apoptosis, and by promoting a metastatic potential. For these reasons, p21 is considered a protein with a dual behavior, with potential benefits, as well as dangerous effects of its expression in malignant cells. Thus, the effectiveness of targeting p21 expression for antitumor therapy needs to be carefully evaluated accordingly. This review summarizes the functions and regulations of p21, and focuses on its involvement in human diseases (particularly cancer), and on the pharmacological approaches to target p21 expression (either positively or negatively) for anticancer therapy. Based on these approaches, the search for new molecules that are able to promote the tumor-suppressor activity, and/or to interfere with the oncogenic properties of p21, could be promising.

Keywords: Anti-cancer target, CDK inhibitor, cell cycle regulator, p21CDKN1A, Apoptosis signal-regulating kinase 1, Base excision repair, Histone Deacetylase, Melanoma differentiation-associated protein 6, Mouse mammary tumor virus, Nucleotide excision repair, Nuclear localization signal, Transcription factor, Wild type p53-activated fragment 1, Translesion DNA synthesis

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Article Details

VOLUME: 12
ISSUE: 2
Year: 2012
Page: [85 - 96]
Pages: 12
DOI: 10.2174/156800912799095126
Price: $58