Tumor-targeted p53-gene therapy enhances the efficacy of conventional chemo/radiotherapy

被引:112
作者
Xu, L
Pirollo, KF
Chang, EH
机构
[1] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Otolaryngol, Washington, DC 20007 USA
[2] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Oncol, Washington, DC 20007 USA
关键词
p53; gene therapy; liposomes; targeting;
D O I
10.1016/S0168-3659(01)00324-8
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A long-standing goal in gene therapy for cancer is a stable, low toxic, systemic gene delivery system that selectively targets tumor cells, including metastatic disease. Progress has been made toward developing non-viral, pharmaceutical formulations of genes for in vivo human therapy, particularly cationic liposome-mediated gene transfer systems. Ligand-directed tumor targeting of cationic liposome-DNA complexes (lipoplexes) is showing promise for targeted gene delivery and systemic gene therapy. Lipoplexes directed by ligands such as folate, transferrin or anti-transferrin receptor scFv, showed tumor-targeted gene delivery and expression in human breast, prostate, head and neck cancers. The two elements, ligand/receptor and liposome composition, work together to realize the goal of functional tumor targeting of gene therapeutics. The tumor suppressor gene, p53, has been shown to be involved in the control of DNA damage-induced apoptosis. Loss or malfunction of this p53-mediated apoptotic pathway has been proposed as one mechanism by which tumors become resistant to chemotherapy or radiation. The systemically delivered ligand-liposome-p53 gene therapeutics resulted in efficient expression of functional wild-type p53, sensitizing the tumors to chemotherapy and radiotherapy. This is a novel strategy combining current molecular medicine with conventional chemotherapy and radiotherapy for the treatment of cancer. The systemic delivery of normal tumor suppressor gene p53 by a non-viral, tumor-targeted delivery system as a new therapeutic intervention has the potential to critically impact the clinical management of cancer. (C) 2001 Elsevier Science B.V. All rights reserved.
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页码:115 / 128
页数:14
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