| Hepatocellular carcinoma (HCC) is the third commonest cause of cancer mortality worldwide, being responsible for over 500000 deaths annually. The median survival of HCC is less than 12 months from diagnosis, reflecting both late diagnosis and lack of effective therapy. Only 10-20% of HCC are suitable for resection at presentation, with a 5 year recurrence-free survival of only 10-20%. Hence, most patients presenting with HCC will eventually develop fast. Since advanced liver cancer lacks effective therapy in most cases, a considerable interest has been drawn towards gene therapy. Therapic genes can be transferred to the tumour, or even distant tissues using a variety of vectors administered by intratumoral or intravascular routes. However, gene therapy for cancer is also faced with a specificity problem: the specific targeting of transgene expression to the site of the tumour. Transcriptional targeting takes advantage of the fact that some cancer cells express a subset of exclusive genes, and uses these cancer-specific promoters to express the desired transgenes.The Human Insulin Like Growth Factor â…¡ (IGF-â…¡) gene is located on chromosome 11p15.5 and spans 30 kb, which includes nine exons and four promoters. A dynamic control of the four promoters (P1-P4) of the IGF-â…¡ gene has been shown in hepatic development. The P3 promoter is active at the fetal stage in liver cells but is repressed after birth and then reappears in most adult human primary liver cancer. Reactivation of the P3 promoter of the IGF-â…¡ gene, resulting in continued expression of IGF-â…¡, was found to be an important driving force of cell proliferation during hepatocarcinogenesis. These data indicated that P3 derived transcripts in autocrine or paracrine stimulated the growth of tumor during tumorigenesis. As a result, The IGF- â…¡ P3 promoter might be a good candidate for targeted HCC cell killing, which can be administered to high IGF-â…¡ expressing cells.
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