Gene Therapy Targeting Receptor-Mediated Cell Death to Cancers

  • Lidong Zhang
  • Bingliang Fang
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Research has demonstrated that delivery of genes encoding tumor necrosis factor (TNF)-α, Fas ligand (FasL), and TNF-related apoptosis-inducing ligand (TRAIL) to tumors can elicit apoptosis in cancer cells and can induce local inflammatory response, leading to regression of cancers. Constitutively active death receptors or chimeric death receptors that can be activated by other ligands, such as vascular endothelial growth factor, have also been exploited for cancer gene therapy. Systemic toxicity of death ligands can be prevented by using genes encoding membrane-bound death ligands and by targeted transgene expression through either targeted transduction or targeted transcription. Improvements have been made for tumor-selective transgene expressions. Various studies have demonstrated that the human telomerase reverse transcriptase promoter, whose gene is active in over 85% of cancers but not in normal cells, can drive tumor-specific transgene expression in a variety of cancer types. Moreover, transgene expression from a tumor-specific promoter can be augmented via transcriptional factors without loss of specificity. Thus far, reported data have shown that targeted expression of TRAIL, FasL, and TNF-α effectively suppressed tumor growth with minimal systemic toxicity. Challenges remain for treatment of metastatic diseases and for overcoming resistances. Here we summarize recent advances in targeted cancer gene therapy with receptor-mediated death pathways.


Gene Therapy Cancer Gene Therapy hTERT Promoter Tumor Necrosis Factor Gene Trail Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Lidong Zhang
    • 1
  • Bingliang Fang
    • 1
  1. 1.Department of Thoracic and Cardiovascular SurgeryThe University of Texas MD Anderson Cancer CenterHouston

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