Cancer therapy vectors Promoters

A great number of tissue-specific promoters has been isolated and characterized, and some of these have been used in experimental cancer gene therapy (see Table 1). Obviously, tissue-specific promoters are also active in the normal tissue from which the tumor originated. Unless the loss of these normal cells is acceptable (as in the case of melanocytes), additional specificity mechanisms need to be considered to make the resulting vector useful for a systemic delivery. This can be achieved, for example, by introducing an additional level of specificity, such as a specificity for proliferating cells or a selectivity for other conditions that are characteristic of tumor cells (see later). 

Other promoters that may be useful for the design of targeted vectors are those induced by disease-specific conditions, such as hypoxia (see Table 1). Thus, a promoter responding to hypoxia through activation by the hypoxia-inducible factor-1 (HIF-1) has been successfully used for experimental cancer gene therapy [69], Disease-specific conditions in tumor cells can also directly result from genetic alterations or from altered signaling pathways. The latter are presumably... 

A. Ido, K. Nakata, Y. Kato, K. Nakao, K. Murata, M. Fujita, N. Ishii, T. Tamaoki, H. Shiku, and S. Nagataki, Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter, Cancer Res. 55 3105 (1995). 

Yamamoto M, Alemany R, Adachi Y, et al. (2001). Characterization of the cyclooxy-genase-2 promoter in an adenoviral vector and its application for the mitigation of toxicity in suicide gene therapy of gastrointestinal cancers. Molec. Ther. 3 385-394. 

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