Methodological approaches in application of synthetic lethality screening towards anticancer therapy

被引:22
作者
Canaani, D. [1 ]
机构
[1] Tel Aviv Univ, Fac Life Sci, Dept Biochem, IL-69978 Tel Aviv, Israel
关键词
chemical synthetic lethality; chemical genetic interactions; genetic synthetic lethality; oncogenes; tumour suppressor genes; RNAi; RNA INTERFERENCE SCREEN; RENAL-CELL CARCINOMA; CULTURED HUMAN-CELLS; DNA-REPAIR; CANCER-CELLS; SACCHAROMYCES-CEREVISIAE; SMALL MOLECULES; TUMOR-CELLS; DRUG; GENE;
D O I
10.1038/sj.bjc.6605000
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A promising direction in the development of selective less toxic cancer drugs is the usage of synthetic lethality concept. The availability of large-scale synthetic low-molecular-weight chemical libraries has allowed HTS for compounds synergistic lethal with defined human cancer aberrations in activated oncogenes or tumour suppressor genes. The search for synthetic lethal chemicals in human/mouse tumour cells is greatly aided by a prior knowledge of relevant signalling and DNA repair pathways, allowing for educated guesses on the preferred potential therapeutic targets. The recent generation of human/rodents genome-wide siRNAs, and shRNA-expressing libraries, should further advance this more focused approach to cancer drug discovery. British Journal of Cancer (2009) 100, 1213-1218. doi: 10.1038/sj.bjc.6605000 www.bjcancer.com Published online 24 March 2009 (C) 2009 Cancer Research UK
引用
收藏
页码:1213 / 1218
页数:6
相关论文
共 43 条
[1]   USE OF A SCREEN FOR SYNTHETIC LETHAL AND MULTICOPY SUPPRESSEE MUTANTS TO IDENTIFY 2 NEW GENES INVOLVED IN MORPHOGENESIS IN SACCHAROMYCES-CEREVISIAE [J].
BENDER, A ;
PRINGLE, JR .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (03) :1295-1305
[2]   Validating cancer drug targets [J].
Benson, John D. ;
Chen, Ying-Nan P. ;
Cornell-Kennon, Susan A. ;
Dorsch, Marion ;
Kim, Sunkyu ;
Leszczyniecka, Magdalena ;
Sellers, William R. ;
Lengauer, Christoph .
NATURE, 2006, 441 (7092) :451-456
[3]   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
[4]   Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase [J].
Bryant, HE ;
Schultz, N ;
Thomas, HD ;
Parker, KM ;
Flower, D ;
Lopez, E ;
Kyle, S ;
Meuth, M ;
Curtin, NJ ;
Helleday, T .
NATURE, 2005, 434 (7035) :913-917
[5]   New approaches to molecular cancer therapeutics [J].
Collins, Ian ;
Workman, Paul .
NATURE CHEMICAL BIOLOGY, 2006, 2 (12) :689-700
[6]   Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells [J].
Dolma, S ;
Lessnick, SL ;
Hahn, WC ;
Stockwell, BR .
CANCER CELL, 2003, 3 (03) :285-296
[7]   Cell-based assays for identification of novel double-strand break-inducing agents [J].
Dunstan, HM ;
Ludlow, C ;
Goehle, S ;
Cronk, M ;
Szankasi, P ;
Evans, DRH ;
Simon, JR ;
Lamb, JR .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2002, 94 (02) :88-94
[8]   shRNA-mediated RNA interference as a tool for genetic synthetic lethality screening in mouse embryo fibroblasts [J].
Einav, Y ;
Agami, R ;
Canaani, D .
FEBS LETTERS, 2005, 579 (01) :199-202
[9]  
Einav Y, 2003, MOL CANCER THER, V2, P1121
[10]   Mitochondriotoxic compounds for cancer therapy [J].
Fantin, V. R. ;
Leder, P. .
ONCOGENE, 2006, 25 (34) :4787-4797