Antisense tumor therapy (a dream under construction).

Cancer, as a genetic disease, is a logical target for gene-oriented therapy--either by replacing the missing/nonfunctioning gene or by depressing the activity of an unwanted gene. The latter is really the inhibition of gene expression using oligonucleotide-based or "antisense" treatment. There are several strategies to achieve this: anti-gene or anti-code with triplex formation; ribozyme with endogenous catalytic RNase activity; antisense with oligonucleotides through steric inhibition or RNaseH activation; and sense strategy to inhibit or trap proteins by nucleic acids. There are two essential partners of the approach: targeted sequence in the unwanted gene/molecule and the complementary antisense oligo (-ribo- or -deoxyribonucleotide). The antisense sequences require chemical modifications (mostly on the phosphodiester backbone, less in the sugar or in the bases) to avoid nucleases, to form complexes for better delivery (in the organism and also in the cell). The activity of the unwanted target should be non-randomly associated with cancer (e.g. abl/ber). Both aspects of antisense treatment require further improvements to get longer lasting and real sequence-specific antitumor effect which could be competitive with the available therapeutic modalities.