期刊
ACTA PHARMACOLOGICA SINICA
卷 40, 期 11, 页码 1373-1385出版社
NATURE PUBL GROUP
DOI: 10.1038/s41401-019-0287-8
关键词
TRAIL; gene delivery; gene therapy; DNA; drug delivery systems; non-viral vectors; cancer therapy
资金
- 973 Program, China [2014CB931900]
- NFSC [81673382, 81521005]
- Strategic Priority Research Program of CAS [XDA12050307]
- National Special Project for Significant New Drugs Development [2018ZX09711002-010-002]
- CAS Scientific Research and Equipment Development Project [YZ201437]
- Fudan-SIMM Joint Research Fund [FU-SIMM20174009]
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a bystander effect of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed.
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