Abstract
The current direction in cancer research is rational drug design, which is based on the evidence that transformed cells are characterized by alterations of genes devoted to the regulation of both cell proliferation and apoptosis. A variety of approaches have been carried out to develop new agents selective for cancer cells. Among these, antisense oligonucleotides (ASOs) are one of such class of new agents able to inhibit specifically the synthesis of a particular cancer-associated protein by binding to protein-encoding RNA, thereby preventing RNA function. In the past decade, several ASOs have been developed and tested in preclinical and clinical studies. Many have shown convincing in vitro reduction in target gene expression and promising activity against a wide variety of tumors. However, because of the multigenic alterations of tumors, the use of ASOs as single agents does not seem to be effective in the treatment of malignancies. Antisense therapy that interferes with signaling pathways involved in cell proliferation and apoptosis are particularly promising in combination with conventional anticancer treatment. An overview of the progress of ASOs used in combination therapy is provided.
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Acknowledgements
We thank Mrs Adele Petricca for her helpful assistance in typing the manuscript. We also thank Dr Barbara Benassi for a critical reading of the manuscript. Work performed in the Experimental Chemotherapy Laboratory was supported by AIRC (Italian Association for Cancer Reserch).
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Biroccio, A., Leonetti, C. & Zupi, G. The future of antisense therapy: combination with anticancer treatments. Oncogene 22, 6579–6588 (2003). https://doi.org/10.1038/sj.onc.1206812
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