Heat-directed suicide gene therapy for breast cancer
- 1 April 2003
- journal article
- Published by Springer Nature in Cancer Gene Therapy
- Vol. 10 (4) , 294-301
- https://doi.org/10.1038/sj.cgt.7700570
Abstract
Adjuvant hyperthermia can improve treatment outcome for locally recurrent breast cancer (LRBC). Previously, we demonstrated that infection of human breast cancer cells with a recombinant adenovirus expressing -galactosidase from the human hsp70b gene promoter (Ad.70b.gal) results in 50- to 800-fold increases in reporter gene expression following heat treatment (30 minutes at 43°C). Here, we describe a heat-directed suicide gene therapy strategy based on an adenoviral vector (Ad.70b.CDTK) in which expression of the dual prodrug-activating E. coli cytosine deaminase/herpes simplex virus thymidine kinase (CDTK) fusion gene is under the control of the hsp70b promoter. Treatment of T47D and MCF-7 breast cancer cells with mild hyperthermia (43°C/30 minutes) and prodrugs (100 g/ml 5-fluorocytosine and 10 g/ml ganciclovir) following infection with Ad.70b.CDTK (10–100 PFU/cell) resulted in 30- to 60-fold decreases in clonogenic survival relative to control cultures treated with heat or prodrugs alone. Clonogenic survival declined even further (up to 240-fold) following heat treatment at 41.5°C for 120 minutes. A decreased clonogenic survival was accompanied by tumor cell apoptosis. These results demonstrate that this combined treatment strategy can be highly effective against heat- and radiation-resistant breast tumor cells and supports the continued development of heat-directed CDTK suicide gene therapy strategies for LRBC.Keywords
This publication has 30 references indexed in Scilit:
- Ionizing radiation but not anticancer drugs causes cell cycle arrest and failure to activate the mitochondrial death pathway in MCF-7 breast carcinoma cellsOncogene, 2001
- Enhancement of Cell Killing by Induction of Apoptosis after Treatment with Mild Hyperthermia at 42°C and CisplatinRadiation Research, 2001
- Replicating adenoviral vector–mediated transfer of a heat-inducible double suicide gene for gene therapyCancer Gene Therapy, 2001
- Eradication of Breast Cancer Xenografts by Hyperthermic Suicide Gene Therapy under the Control of the Heat Shock Protein PromoterHuman Gene Therapy, 2000
- Heat-directed gene targeting of adenoviral vectors to tumor cellsCancer Gene Therapy, 2000
- A Novel, Conditionally Replicative Adenovirus for the Treatment of Breast Cancer That Allows Controlled Replication of E1a-Deleted Adenoviral VectorsHuman Gene Therapy, 2000
- Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigenJournal of Clinical Investigation, 2000
- Differential chemosensitivity of breast cancer cells to ganciclovir treatment following adenovirus-mediated herpes simplex virus thymidine kinase gene transferCancer Gene Therapy, 1999
- Protein Glycosylation in a Heat-Resistant Rat Fibroblast Cell Model Expressing Human HSP70Biochemical and Biophysical Research Communications, 1997
- Thermal Protein Denaturation and Protein Aggregation in Cells Made Thermotolerant by Various Chemicals: Role of Heat Shock ProteinsExperimental Cell Research, 1995