Genetic prodrug activation therapy for breast cancer: A phase I clinical trial of erbB-2-directed suicide gene expression.
J Clin Oncol
; 17(7): 2180-9, 1999 Jul.
Article
en En
| MEDLINE
| ID: mdl-10561274
ABSTRACT
PURPOSE:
This trial was designed to test the safety and efficacy of a tumor-specific genetic prodrug activation therapy targeted by use of the human erbB-2 gene promoter. The erbB-2 oncogene is overexpressed in approximately 20% of cases of breast cancer and is associated with poor prognosis. PATIENTS ANDMETHODS:
Twelve breast cancer patients received transcriptionally targeted gene therapy in a phase I clinical trial using direct intratumoral injection of plasmid construct combined with systemic administration of prodrug. The genetic prodrug activation therapy is specifically targeted to erbB-2-overexpressing breast cancer cells by use of a therapeutic cassette that contains the Escherichia coli cytosine deaminase gene driven by the tumor-specific erbB-2 promoter, thus allowing activation of fluorocytosine to the active cytotoxic fluorouracil only within tumor cells that express the oncogene.RESULTS:
The approach was shown to be safe and to result in targeted gene expression in up to 90% of cases. Using a number of different assays, we demonstrated that significant levels of expression of the suicide gene were specifically restricted to erbB-2-positive tumor cells, confirming the selectivity of the approach.CONCLUSION:
The results of this study, the first targeted gene therapy for breast cancer and the first to use the cytosine deaminase system in human subjects, are encouraging for the development of genetic prodrug activation therapies that exploit the transcriptional profile of cancer cells.
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Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Profármacos
/
Terapia Genética
/
Regulación Neoplásica de la Expresión Génica
/
Genes erbB-2
/
Fluorouracilo
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Año:
1999
Tipo del documento:
Article