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 target s for cancer therapy. Antisense nucleic acids can be used to modulate the e xpression of selected genes, and to suppress malignant behaviour in cancer cells. Nevertheless, in practice, the selection of suitable antisense targe ts still remains a trial-and-error procedure. Promising targets for antisen se cancer therapy that have been extensively studied include proteases and protease receptors, telomerase, fusion genes, the Eel family of proteins an d various protein kinases. Combinations of antisense oligonucleotides with cytotoxic agents offer important advantages in cancer therapy. However, con trol oligonucleotides must be carefully chosen to separate the antisense ef fect from the many potential nonspecific effects. Several antisense drugs h ave been very effective in in vitro experiments, and have entered clinical trials. Successive generations of antisense drugs, including: molecules wit h novel backbones or other structural modifications, chimeric : oligonucleo tides and peptide nucleic acids, are currently in development.