Therapeutic targeting of p53 by small molecules

被引:70
作者
Selivanova, Galina [1 ]
机构
[1] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
p53; Small molecules; Anti-cancer therapy; Apoptosis; Growth arrest; PRIMA-1 INDUCES APOPTOSIS; TUMOR-SUPPRESSOR FUNCTION; DNA-DAMAGE RESPONSE; C-TERMINAL PEPTIDE; CELL-CYCLE-ARREST; MUTANT P53; IN-VITRO; GROWTH ARREST; CANCER-CELLS; EMBRYONIC LETHALITY;
D O I
10.1016/j.semcancer.2010.02.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aberrant p53 function is one of the major requirements for tumor development. Reactivation of p53 function by small molecules is a promising strategy to combat cancer due to potent tumor suppressor activities of p53. Recent developments in p53 biology reveal that manipulation of p53 function might pave way to a long cancer-free life. A number of small molecules which rescue p53 function by different mechanisms, acting upstream of p53 or targeting the p53 protein itself have been identified. Notably, these molecules trigger different biological outcomes, suggesting that it might be feasible to direct p53-mediated response in a desired way. In this review I discuss the latest developments in the search for small molecules which rescue p53 function by targeting the p53 protein. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:46 / 56
页数:11
相关论文
共 104 条
[1]  
Abarzua P, 1996, ONCOGENE, V13, P2477
[2]   Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma [J].
Amaravadi, Ravi K. ;
Yu, Duonan ;
Lum, Julian J. ;
Bui, Thi ;
Christophorou, Maria A. ;
Evan, Gerard I. ;
Thomas-Tikhonenko, Andrei ;
Thompson, Craig B. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (02) :326-336
[3]   Caspase 2 is both required for p53-mediated apoptosis and downregulated by p53 in a p21-dependent manner [J].
Baptiste-Okoh, Nicole ;
Barsotti, Anthony M. ;
Prives, Carol .
CELL CYCLE, 2008, 7 (09) :1133-1138
[4]   DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis [J].
Bartkova, J ;
Horejsi, Z ;
Koed, K ;
Krämer, A ;
Tort, F ;
Zieger, K ;
Guldberg, P ;
Sehested, M ;
Nesland, JM ;
Lukas, C ;
Orntoft, T ;
Lukas, J ;
Bartek, J .
NATURE, 2005, 434 (7035) :864-870
[5]   Structural and Functional Basis for Therapeutic Modulation of p53 Signaling [J].
Bassett, Emily A. ;
Wang, Wenge ;
Rastinejad, Farzan ;
El-Deiry, Wafik S. .
CLINICAL CANCER RESEARCH, 2008, 14 (20) :6376-6386
[6]   Regression of progestin-accelerated 7,12-dimethylbenz[a]anthracene-induced mammary tumors in Sprague-Dawley rats by p53 reactivation and induction of massive apoptosis: a pilot study [J].
Benakanakere, Indira ;
Besch-Williford, Cynthia ;
Ellersieck, Mark R. ;
Hyder, Salman M. .
ENDOCRINE-RELATED CANCER, 2009, 16 (01) :85-98
[7]   TP53 status and response to chemotherapy in breast cancer [J].
Bertheau, Philippe ;
Espie, Marc ;
Turpin, Elisabeth ;
Lehmann, Jacqueline ;
Plassa, Louis-Francois ;
Varna, Mariana ;
Janin, Anne ;
de The, Hugues .
PATHOBIOLOGY, 2008, 75 (02) :132-139
[8]   Targeted rescue of a destabilized mutant of p53 by an in silico screened drug [J].
Boeckler, Frank M. ;
Joerger, Andreas C. ;
Jaggi, Gaurav ;
Rutherford, Trevor J. ;
Veprintsev, Dmitry B. ;
Fersht, Alan R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (30) :10360-10365
[9]   Conditional RNA interference in vivo to study mutant p53 oncogenic gain of function on tumor malignancy [J].
Bossi, Gianluca ;
Marampon, Francesco ;
Maor-Aloni, Revital ;
Zani, Bianca ;
Rotter, Varda ;
Oren, Moshe ;
Strano, Sabrina ;
Blandino, Giovanni ;
Sacchi, Ada .
CELL CYCLE, 2008, 7 (12) :1870-1879
[10]   Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD [J].
Budanov, AV ;
Sablina, AA ;
Feinstein, E ;
Koonin, EV ;
Chumakov, PM .
SCIENCE, 2004, 304 (5670) :596-600