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Combining Radiotherapy with Gene Therapy (From the Bench to the Bedside): A Novel Treatment Strategy for Prostate Cancer

^a Baylor College of Medicine, ^b The Methodist Hospital, and ^c Veterans Affairs Medical Center, Houston, Texas, USA; ^d Harvard Gene Therapy Initiative, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Bin S. Teh, M.D., The Methodist Hospital, Radiotherapy Department, 6565 Fannin, MS 121-B, Houston, Texas 77030, USA. Telephone: 713-790-2637; Fax: 713-793-1300; e-mail: bteh{at}bcm.tmc.edu

Combined radiotherapy and gene therapy is a novel therapeutic approach for prostate cancer. There are various potential benefits in combining ionizing radiation with gene therapy to achieve enhanced antitumor effects: A) ionizing radiation improves transfection/ transduction efficiency, transgene integration, and possibly, the "bystander effect" of gene therapy; B) gene therapy, on the other hand, may interfere with repair of radiation-induced DNA damage and increase DNA susceptibility to radiation damage in cancer cells, and C) radiotherapy and gene therapy target at different parts of the cell cycle. Preclinical data have demonstrated the enhanced antitumor effects of this combined approach in local tumor control, prolongation of survival, as well as systemic control. This combined radio-gene therapy is under study in an ongoing clinical trial in prostate cancer. Our study adds gene therapy to the standard of care therapy (radiotherapy). These treatment modalities have different toxicity profiles. The goal of this combined approach is to enhance cancer cure without an increase in treatment-related toxicity. This approach also offers a new paradigm in spatial cooperation, whereby two local therapies are combined to elicit both local and systemic effects. Early clinical results showed the safety of this approach.

Key Words. Radiotherapy • Gene therapy • Prostatic neoplasms • Treatment

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