Therapeutic exploitation of the p53 pathway

被引:103
作者
Lane, DP [1 ]
Lain, S [1 ]
机构
[1] Univ Dundee, Dept Surg & Mol Oncol, Dundee DD1 9SY, Scotland
关键词
D O I
10.1016/S1471-4914(02)02309-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Analysis of the gene encoding p53 could serve to evaluate the effectiveness of a cancer treatment. Mutations in this gene occur in half of all human cancers, and regulation of the protein is defective in a variety of others. Novel strategies that exploit our knowledge of the function and regulation of p53 are being actively investigated. Strategies directed at treating tumours that have p53 mutations include gene therapy, viruses that only replicate in p53 deficient cells, and the search for small molecules that reactivate mutant p53. Potentiating the function of p53 in a non-genotoxic way in tumours that express wildtype protein can be achieved by inhibiting the expression and function of Mdm2 or viral oncoproteins.
引用
收藏
页码:S38 / S42
页数:5
相关论文
共 33 条
[1]   An adenovirus mutant that replicates selectively in p53-deficient human tumor cells [J].
Bischoff, JR ;
Kim, DH ;
Williams, A ;
Heise, C ;
Horn, S ;
Muna, M ;
Ng, L ;
Nye, JA ;
SampsonJohannes, A ;
Fattaey, A ;
McCormick, F .
SCIENCE, 1996, 274 (5286) :373-376
[2]  
Blatt RJR, 1999, J BIOLAW BUS, V2, P3
[3]   Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo [J].
Bottger, A ;
Bottger, V ;
Sparks, A ;
Liu, WL ;
Howard, SF ;
Lane, DP .
CURRENT BIOLOGY, 1997, 7 (11) :860-869
[4]  
Bottger V, 1996, ONCOGENE, V13, P2141
[5]   Checkpoints: How to activate p53 [J].
Caspari, T .
CURRENT BIOLOGY, 2000, 10 (08) :R315-R317
[6]   The p53-deficient mouse: A model for basic and applied cancer studies [J].
Donehower, LA .
SEMINARS IN CANCER BIOLOGY, 1996, 7 (05) :269-278
[7]   Pharmacological rescue of mutant p53 conformation and function [J].
Foster, BA ;
Coffey, HA ;
Morin, MJ ;
Rastinejad, F .
SCIENCE, 1999, 286 (5449) :2507-2510
[8]   Functions of the MDM2 oncoprotein [J].
Freedman, DA ;
Wu, L ;
Levine, AJ .
CELLULAR AND MOLECULAR LIFE SCIENCES, 1999, 55 (01) :96-107
[9]   A peptide that binds and stabilizes p53 core domain:: Chaperone strategy for rescue of oncogenic mutants [J].
Friedler, A ;
Hansson, LO ;
Veprintsev, DB ;
Freund, SMV ;
Rippin, TM ;
Nikolova, PV ;
Proctor, MR ;
Rüdiger, S ;
Fersht, AR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (02) :937-942
[10]   Tumor-specific mutations in p53: The acid test [J].
Hainaut, P .
NATURE MEDICINE, 2002, 8 (01) :21-23