Combining radiotherapy with gene therapy (from the bench to the bedside): a novel treatment strategy for prostate cancer.
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.
Teh
Bin S
BS
Baylor College of Medicine, Houston, Texas 77030, USA. bteh@bcm.tmc.edu
Aguilar-Cordova
Estuardo
E
Vlachaki
Maria T
MT
Aguilar
Laura
L
Mai
Wei-Yuan
WY
Caillouet
James
J
Davis
Maria
M
Miles
Brian
B
Kadmon
Dov
D
Ayala
Gustavo
G
Lu
Hsin H
HH
Chiu
J Kam
JK
Carpenter
L Steven
LS
Woo
Shiao Y
SY
Grant
Walter H
WH
Wheeler
Thomas
T
Thompson
Timothy C
TC
Butler
E Brian
EB
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003131:Combined Modality Therapy; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018139:Simplexvirus / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D015774:Ganciclovir