Cancer gene therapy: Combination with radiation therapy and the role of bystander cell killing in the anti-tumor effect

Katalin Lumniczky, G. Sáfrány

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Current anti-cancer modalities such as surgery, chemo- and radiation therapies have only limited success in cancer treatment. Gene therapy is a promising new tool to improve outcomes. In this review, first we summarize the various strategies to kill tumor cells, and then focus on the bystander effect of gene therapy. A variety of strategies, such as gene-directed enzyme pro-drug therapy, activation of an anti-tumor immune attack, application of replication-competent and oncolytic viral vectors, tumor-specific as well as radiation- and hypoxia-induced gene expression, might be applied to target tumor cells. We put special emphasis on the combination of these approaches with local tumor irradiation. Using the available vector systems, only a small portion of cancer cells contains the therapeutic genes under clinical situations. However, cells directly targeted by gene therapy will transfer death signals to neighboring cancer cells. This bystander cell killing improves the efficiency of cancer gene therapy. Death signals are delivered by cell-to-cell communication through gap junction intercellular contacts, release of toxic metabolites into the neighborhood or to larger distances, phagocytosis of apoptotic bodies, and the activation of the immune system. Bystander cell killing can be enhanced by the introduction of gap junction proteins into cells, by further activating the immune system with immune-stimulatory molecules, or by introducing genes that help the transfer of cytotoxic genes and/or metabolites into bystander cells. In conclusion, although bystander cell killing can improve therapeutic effects, there should be additional developments in cancer gene therapy for a more efficient clinical application.

Original languageEnglish
Pages (from-to)118-124
Number of pages7
JournalPathology and Oncology Research
Volume12
Issue number2
DOIs
Publication statusPublished - 2006

Fingerprint

Neoplasm Genes
Genetic Therapy
Radiotherapy
Neoplasms
Genes
Immune System
Bystander Effect
Connexins
Poisons
Gap Junctions
Prodrugs
Therapeutic Uses
Phagocytosis
Cell Communication
Radiation
Gene Expression
Drug Therapy

Keywords

  • Bystander effect
  • Gap junction
  • Gene therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pathology and Forensic Medicine

Cite this

Cancer gene therapy : Combination with radiation therapy and the role of bystander cell killing in the anti-tumor effect. / Lumniczky, Katalin; Sáfrány, G.

In: Pathology and Oncology Research, Vol. 12, No. 2, 2006, p. 118-124.

Research output: Contribution to journalArticle

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