Molecular approaches to chemo-radiotherapy
Section snippets
Combination gene therapy and radiotherapy
Radiotherapy is the treatment modality of choice for most solid malignancies. However, the tolerance of surrounding normal tissues to treatment-induced injury often restricts the dose that can be delivered to the tumour to achieve cure. This problem can be partly overcome using physical techniques such as conformal or intensity modulated radiotherapy that deliver the dose to a more precisely defined tumour volume. An alternative approach is to combine radiotherapy with a pharmacological- or
Radiation-mediated gene therapy (RMGT)
Radiation-mediated gene therapy exploits the fact that in the majority of patients receiving radiotherapy the radiation is directed to the tumour volume, providing some degree of tumour localisation for controlling the expression of therapeutic genes. Temporal and spatial control of gene expression can therefore be achieved for any genes delivered to the tumour and for any tumour types treated with radiotherapy 5, 6, 7.
Hypoxia-mediated gene therapy
The presence of hypoxia is a negative prognostic indicator for outcome following radiotherapy in a range of human tumour sites 59, 60, 61, 62, 63. The absence of a cell killing component that can be attributed to radiation-mediated oxygen radicals is unlikely to be the only reason for the resistance of hypoxic tissue to the lethal effects of radiotherapy [64]. Resistance may also arise from modifications to gene expression induced as a direct consequence of the hypoxic environment, such as a
Other gene therapy approaches
A number of radiotherapy and gene therapy strategies have been developed. High therapeutic potential was recently demonstrated for radiation therapy in combination with a trimodal approach consisting of a replication-competent oncolytic adenovirus containing a cytosine deaminase/HSVtk fusion gene [42]. This combination of radiation therapy, lytic viral therapy and double suicide gene therapy produced significant tumour regression in an experimental C33A tumour xenograft model.
Manipulating the
Acknowledgements
BM and SDS were supported by grants from the UK Cancer Research Campaign.
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Applications of tissue-specific and cancer-selective gene promoters for cancer diagnosis and therapy
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2005, Radiologic Clinics of North AmericaResveratrol-responsive CArG elements from the Egr-1 promoter for the induction of GADD45α to arrest the G2/M transition
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2015, Journal of Clinical and Diagnostic Research
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Now at: Department of Radiation Oncology, Wayne State University and Karmanos Cancer Institute, 4100 John R. Detroit, MI 48210, USA.