Enhanced radiation response through directed molecular targeting approaches

Spencer J. Collis, Theodore L. DeWeese

Research output: Contribution to journalReview article

Abstract

In both the pre- and post-human genome sequencing eras, there has been an increase in the understanding of the molecular mechanisms influencing cellular sensitivity to DNA damaging agents such as ionizing radiation. Out of this work have arisen many cellular factors that could be specifically targeted, at the molecular level, to alter the functionality of a single protein or pathway involved in the response to radiation damage as a means to increase cell killing following radiation treatment. As such, there are many promising new combination radio-gene therapy approaches being developed and assessed in pre-clinical and clinical studies for several different malignancies. Combination of such modalities aims to increase the therapeutic index, giving rise to increased tumor cell killing with a simultaneous reduction in normal cell toxicity. Restricted delivery and/or targeting modalities combined with conformal radiotherapy regimes could provide significant local control of tumors, impeding their development into metastatic disease, which poses a greater challenge for palliative and curative treatments. This review will summarize current and novel gene therapy strategies that are being developed aimed at enhancing the effects of radiotherapy through the use of directed molecular targeting approaches.

Original languageEnglish (US)
Pages (from-to)277-292
Number of pages16
JournalCancer and Metastasis Reviews
Volume23
Issue number3-4
DOIs
StatePublished - Aug 1 2004

Keywords

  • DNA damage and repair
  • gene therapy
  • ionizing radiation
  • molecular targeting
  • radiosensitivity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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