| Though there have been some achievements during the war between human beings and cancer, the complexity of molecular mechanisms of carcinogenesis (multigene, multistage and multitype) has made this process to be long and hard.This study systematically analyzed the current R & D status of anticancer drugs including cytotoxic chemotherapy drugs, biotherapy drugs and gene therapy drugs. The advantages and disadvantages of these drugs have been analyzed on side of effectiveness and safety. It has been put forward that the key problem for human beings to overcome cancer is that the specific targets have not been found. Furthermore, the current status of new anticancer drug development targets has been analyzed.The causality of gene, protein and phenotype in cancer has been analyzed. It has been put forward that transcription factor DECOY approach may serve as a novel therapeutic strategy for cancer therapy. To find the suitable transcription factor targets and systematically study the regulation relationship of the genes, human genome regulation database has been built up making advantages of the achievement in human genome project. Totally 1532 human transcription factors as well as the structures and functions of downstream 1607 genes have been included. Furthermore, the relationship between these transcription factors, genes and cancer phenotypes has been annotated. The dynamic single gene centered network and single function centered multigene regulation network make it easy to understand the regulation relationship between different genes. It provides an important and convenient tool for the discovery of new drug targets.It has been introduced in this study how to predict new drug discovery targets using this database by giving the example of cancer cell phenotype related to cell proliferation. Furthermore, the method to design DECOY nucleotides drugs has been introduced making advantages of the 3-D structure of the targeted transcription factor provided by the database.To prove the feasibility of this creative strategy in cancer treatment, thefollowing studies have been fulfilled.? Synthesis and purification of DECOY nucleotides in small and moderate scale. Quality control method has been preliminarily studied. Qualified DECOY nucleotides in small and moderate scale have been gained.? Gel shift assay proved that K102 was able to specifically bind to transcription factor. K102 could induce apoptosis of cancer cells. Absorption of fluorescence labeled K102 showed that over 90% DECOY drugs could penetrate into the cell nucleus with the help of liposome carrier.? MTT assay was adopted to screen the in vitro anticancer activity of DECOY nucleotides drugs. DECOY nucleotides such as K102 and K206 were found to inhibit the proliferation of different cancer cells including non-small cell lung cancer, liver cancer, breast cancer and glioma.? K102 showed obvious anticancer activity in nude mice xenograft model. Furthermore, the very low toxicity of K102 has proved that it is very safe.The above studies have proved that transcription factor DECOY approach is practical for cancer therapy. The transcription factor targets predicted by the human genome regulation database are applicable.To make preparation for DECOY nucleotides drugs development, the structure and pharmaceutical of K102 have been optimized. It is proved that the partially sulfur substituted K102 is the ideal structure and the cation liposome is the ideal pharmaceutical carrier.Creative points:1. Strategy for the discovery and development of anticancer new drugs has been put forward, i.e., targeting the transcription factor for the upstream control of cancer cell phenotype to treat cancer. Furthermore, this transcription factor DECOY approach has been proved to be successful at molecular, cellular and animal level.2. Human genomic transcription factor database has been created which can be used for target prediction and new drug design. Characters of this database:? Creative in the aims and approaches. This database i...
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