Targeting cancer by transcriptional control in cancer gene therapy and viral oncolysis

被引:111
作者
Dorer, Dominik E.
Nettelbeck, Dirk M. [1 ]
机构
[1] Helmholtz Univ, Grp Oncolyt Adenoviruses, German Canc Res Ctr, D-69120 Heidelberg, Germany
关键词
Oncolytic virus; Tissue-/tumor-specific promoter; Virotherapy; Targeted therapy; Pan-cancer promoter; Gene transfer vector; CONDITIONALLY REPLICATIVE ADENOVIRUS; SQUAMOUS-CELL CARCINOMA; HERPES-SIMPLEX-VIRUS; HUMAN-PAPILLOMAVIRUS TYPE-16; TUMOR-SELECTIVE REPLICATION; TISSUE-SPECIFIC EXPRESSION; FIBRILLARY ACIDIC PROTEIN; SODIUM-IODIDE SYMPORTER; GROWTH-FACTOR RECEPTOR; SINGLE-CHAIN ANTIBODY;
D O I
10.1016/j.addr.2009.03.013
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Cancer-specificity is the key requirement for a drug or treatment regimen to be effective against malignant disease-and has rarely been achieved adequately to date. Therefore, targeting strategies need to be implemented for future therapies to ensure efficient activity at the site of patients' tumors or metastases without causing intolerable side-effects. Gene therapy and viral oncolysis represent treatment modalities that offer unique opportunities for tumor targeting. This is because both the transfer of genes with anticancer activity and viral replication-induced cell killing, respectively, facilitate the incorporation of multiple mechanisms restricting their activity to cancer. To this end, cellular mechanisms of gene regulation have been successfully exploited to direct therapeutic gene expression and viral cell lysis to cancer cells. Here, transcriptional targeting has been the role model and most widely investigated. This approach exploits cellular gene regulatory elements that mediate cell type-specific transcription to restrict the expression of therapeutic genes or essential viral genes, ideally to cancer cells. In this review, we first discuss the rationale for such promoter targeting and its limitations. We then give an overview how tissue-/tumor-specific promoters are being identified and characterized. Strategies to apply and optimize such promoters for the engineering of targeted viral gene transfer vectors and oncolytic viruses-with respect to promoter size, selectivity and activity in the context of viral genomes-are described. Finally, we discuss in more detail individual examples for transcriptionally targeted virus drugs. First highlighting oncolytic viruses targeted by prostate-specific promoters and by the telomerase promoter as representatives of tissue-targeted and pan-cancer-specific virus drugs respectively, and secondly recent developments of the last two years. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:554 / 571
页数:18
相关论文
共 216 条
[1]
Adachi Y, 2001, CANCER RES, V61, P7882
[2]
Real-time diagnostic imaging of tumors and metastases by use of a replication-competent herpes vector to facilitate minimally invasive oncological surgery [J].
Adusumilli, Prasad S. ;
Stiles, Brendon M. ;
Chan, Mei-Ki ;
Eisenberg, David P. ;
Yu, Zhenkun ;
Stanziale, Stephen F. ;
Huq, Rumana ;
Wong, Richard J. ;
Rusch, Valerie W. ;
Fong, Yuman .
FASEB JOURNAL, 2006, 20 (02) :726-+
[3]
A conditionally replicating adenovirus targeted to tumor cells through activated RAS/P-MAPK-selective mRNA stabilization [J].
Ahmed, A ;
Thompson, J ;
Emiliusen, L ;
Murphy, S ;
Beauchamp, RD ;
Suzuki, K ;
Alemany, R ;
Harrington, K ;
Vile, RG .
NATURE BIOTECHNOLOGY, 2003, 21 (07) :771-777
[4]
Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter [J].
Ahn, M. ;
Lee, S-J ;
Li, X. ;
Jimenez, J. A. ;
Zhang, Y-P ;
Bae, K-H ;
Mohammadi, Y. ;
Kao, C. ;
Gardner, T. A. .
CANCER GENE THERAPY, 2009, 16 (01) :73-82
[5]
Replicative adenoviruses for cancer therapy [J].
Alemany, R ;
Balagué, C ;
Curiel, DT .
NATURE BIOTECHNOLOGY, 2000, 18 (07) :723-727
[6]
[Anonymous], 2007, Global Cancer Facts Figures
[7]
STRUCTURAL AND TRANSCRIPTIONAL ANALYSIS OF HUMAN PAPILLOMAVIRUS TYPE-16 SEQUENCES IN CERVICAL-CARCINOMA CELL-LINES [J].
BAKER, CC ;
PHELPS, WC ;
LINDGREN, V ;
BRAUN, MJ ;
GONDA, MA ;
HOWLEY, PM .
JOURNAL OF VIROLOGY, 1987, 61 (04) :962-971
[8]
Human papillomavirus E6E7-mediated adenovirus cell killing:: Selectivity of mutant adenovirus replication in organotypic cultures of human keratinocytes [J].
Balagué, C ;
Noya, F ;
Alemany, R ;
Chow, LT ;
Curiel, DT .
JOURNAL OF VIROLOGY, 2001, 75 (16) :7602-7611
[9]
Banerjee NS, 2004, MOL CANCER THER, V3, P437
[10]
Dual targeting of adenoviral vectors at the levels of transduction and transcription enhances the specificity of gene expression in cancer cells [J].
Barnett, BG ;
Tillman, BW ;
Curiel, DT ;
Douglas, JT .
MOLECULAR THERAPY, 2002, 6 (03) :377-385