This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Curtin, J. F. Articles by Castro, M. G. Search for Related Content PubMed PubMed Citation Articles by Curtin, J. F. Articles by Castro, M. G. Related Collections Therapeutics and Targets Therapeutics and Targets: Experimental Therapeutics– Biologics

Review

Turning the gene tap off; implications of regulating gene expression for cancer therapeutics

Board of Governors Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, and Departments of Molecular and Medical Pharmacology and Medicine, Jonsson Comprehensive Cancer Center; Brain Research Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California

Requests for reprints: Maria G. Castro, University of California-Los Angeles and Cedars Sinai Medical Center, 8700 Beverly Boulevard, Davis Building 5090, Los Angeles, CA 90048. Phone: 310-423-7303; Fax: 310-423-7308. E-mail: castromg{at}cshs.org

Cancer poses a tremendous therapeutic challenge worldwide, highlighting the critical need for developing novel therapeutics. A promising cancer treatment modality is gene therapy, which is a form of molecular medicine designed to introduce into target cells genetic material with therapeutic intent. Anticancer gene therapy strategies currently used in preclinical models, and in some cases in the clinic, include proapoptotic genes, oncolytic/replicative vectors, conditional cytotoxic approaches, inhibition of angiogenesis, inhibition of growth factor signaling, inactivation of oncogenes, inhibition of tumor invasion and stimulation of the immune system. The translation of these novel therapeutic modalities from the preclinical setting to the clinic has been driven by encouraging preclinical efficacy data and advances in gene delivery technologies. One area of intense research involves the ability to accurately regulate the levels of therapeutic gene expression to achieve enhanced efficacy and provide the capability to switch gene expression off completely if adverse side effects should arise. This feature could also be implemented to switch gene expression off when a successful therapeutic outcome ensues. Here, we will review recent developments related to the engineering of transcriptional switches within gene delivery systems, which could be implemented in clinical gene therapy applications directed at the treatment of cancer. [Mol Cancer Ther 2008;7(3):439–48]

¹ http://www.oralcancerfoundation.org/news/story.asp?newsId=1033

Received 11/26/07; revised 1/11/08; accepted 1/18/08.