Tissue Specific Promoters in Colorectal Cancer

Abstract

Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

Figure 1

Schematic representation of a colon cancer specific promoter and the induction of therapeutic gene expression. High levels of specific transcription factors in colon cancer cells are able to induce therapeutic gene expression. By contrast, no expression of these specific transcription factors in normal colon cells avoids the transcription of the therapeutic gene.

Figure 2

Antitumor effect of the E gene under CEA promoter. The high transcriptional activity of the CEA promoter in colon cancer cells leads to E gene expression which encodes a cytotoxic protein. The protein E targets mitochondria in colon cancer cells, disrupting their cristae and inducing apoptosis by release of cytochrome c and activation of caspases 9 and 3.