The genetics of the p53 pathway, apoptosis and cancer therapy

被引:554
作者
Vazquez, Alexei [1 ]
Bond, Elisabeth E. [3 ]
Levine, Arnold J. [1 ,2 ]
Bond, Gareth L. [3 ]
机构
[1] Inst Adv Study, Princeton, NJ 08540 USA
[2] Canc Inst New Jersey, New Brunswick, NJ 08903 USA
[3] Univ Oxford, Ludwig Inst Canc Res, Oxford OX3 7DQ, England
关键词
D O I
10.1038/nrd2656
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The p53 pathway has been shown to mediate cellular stress responses; p53 can initiate DNA repair, cell-cycle arrest, senescence and, importantly, apoptosis. These responses have been implicated in an individual's ability to suppress tumour formation and to respond to many types of cancer therapy. Here we focus on how best to use knowledge of this pathway to tailor current therapies and develop novel ones. Studies of the genetics of p53 pathway components-in particular p53 itself and its negative regulator MDM2-in cancer cells has proven useful in the development of targeted therapies. Furthermore, inherited single nucleotide polymorphisms in p53 pathway genes could serve a similar purpose.
引用
收藏
页码:979 / 987
页数:9
相关论文
共 84 条
[71]   Polymorphism in wild-type p53 modulates response to chemotherapy in vitro and in vivo [J].
Sullivan, A ;
Syed, N ;
Gasco, M ;
Bergamaschi, D ;
Trigiante, G ;
Attard, M ;
Hiller, L ;
Farrell, PJ ;
Smith, P ;
Lu, X ;
Crook, T .
ONCOGENE, 2004, 23 (19) :3328-3337
[72]  
Thomas M, 1999, MOL CELL BIOL, V19, P1092
[73]   Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy [J].
Tovar, C ;
Rosinski, J ;
Filipovic, Z ;
Higgins, B ;
Kolinsky, K ;
Hilton, H ;
Zhao, XL ;
Vu, BT ;
Qing, WG ;
Packman, K ;
Myklebost, O ;
Heimbrook, DC ;
Vassilev, LT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (06) :1888-1893
[74]   MDM2 SNP 309 and p53 codon 72 polymorphisms are associated with the outcome of oral carcinoma patients receiving postoperative irradiation [J].
Tu, Hsi-Feng ;
Chen, Hong-Wen ;
Kao, Shou-Yen ;
ina, Shu-Chun ;
Liu, Chung-Ji ;
Chang, Kuo-Wei .
RADIOTHERAPY AND ONCOLOGY, 2008, 87 (02) :243-252
[75]   In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 [J].
Vassilev, LT ;
Vu, BT ;
Graves, B ;
Carvajal, D ;
Podlaski, F ;
Filipovic, Z ;
Kong, N ;
Kammlott, U ;
Lukacs, C ;
Klein, C ;
Fotouhi, N ;
Liu, EA .
SCIENCE, 2004, 303 (5659) :844-848
[76]   MDM2 inhibitors for cancer therapy [J].
Vassilev, Lyubomir T. .
TRENDS IN MOLECULAR MEDICINE, 2007, 13 (01) :23-31
[77]   Restoration of p53 function leads to tumour regression in vivo [J].
Ventura, Andrea ;
Kirsch, David G. ;
McLaughlin, Margaret E. ;
Tuveson, David A. ;
Grimm, Jan ;
Lintault, Laura ;
Newman, Jamie ;
Reczek, Elizabeth E. ;
Weissleder, Ralph ;
Jacks, Tyler .
NATURE, 2007, 445 (7128) :661-665
[78]   Evaluation of the combined effect of p53 codon 72 polymorphism and hotspot mutations in response to anticancer drugs [J].
Vikhanskaya, F ;
Siddique, MM ;
Lee, MK ;
Broggini, M ;
Sabapathy, K .
CLINICAL CANCER RESEARCH, 2005, 11 (12) :4348-4356
[79]   Live or let die: The cell's response to p53 [J].
Vousden, KH ;
Lu, X .
NATURE REVIEWS CANCER, 2002, 2 (08) :594-604
[80]   Restoration of p53 to limit tumor growth [J].
Wang, Wenge ;
Ei-Deiry, Wafik S. .
CURRENT OPINION IN ONCOLOGY, 2008, 20 (01) :90-96