Antisense oligonucleotides in cancer: recent advances.
The activation of dominant oncogenes and inactivation of tumour suppressor genes may result in cancer. These genetic events may represent novel targets for cancer therapy. Antisense nucleic acids can be used to modulate the expression of selected genes, and to suppress malignant behaviour in cancer cells. Nevertheless, in practice, the selection of suitable antisense targets still remains a trial-and-error procedure. Promising targets for antisense cancer therapy that have been extensively studied include proteases and protease receptors, telomerase, fusion genes, the Bcl family of proteins and various protein kinases. Combinations of antisense oligonucleotides with cytotoxic agents offer important advantages in cancer therapy. However, control oligonucleotides must be carefully chosen to separate the antisense effect from the many potential nonspecific effects. Several antisense drugs have been very effective in in vitro experiments, and have entered clinical trials. Successive generations of antisense drugs, including molecules with novel backbones or other structural modifications, chimeric oligonucleotides and peptide nucleic acids, are currently in development.
Dept of Medicine, Columbia University, College of Physicians & Surgeons, New York, New York 10032, USA.
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