Antisense reagents and technology have developed as extraordinarily useful tools for analysis of gene function. The capacity of antisense to reduce expression of RNA (including protein-encoding mRNA and non-coding RNA) important in a multitude of diseases (including cancer) has led to the concept of using antisense molecules as drugs to treat those diseases. Both antisense RNA (RNAi) and antisense oligonucleotides (ASOs) are being developed for this purpose, with ASOs currently the most advanced in clinical testing. ASOs inhibit translation or induce degradation of complementary target RNA, and both Phase I and Phase II trials are either completed or in progress for a number of diseases. In this review, we focus on antisense approaches to treatment of two cancers (melanoma and hormone-resistant prostate cancer) where the early application of ASOs has provided important information revealing both potential for success and lessons for future preclinical and clinical investigation of ASOs as anti-cancer drugs. The progress of clinical application of two ASOs showing promise in treatment of human cancers –– Oblimersen(G3139), targeting BCL2 for the treatment of metastatic melanoma, and Custirsen (OGX-11), targeting clusterin for the treatment of hormone refractory prostate cancer (HRPC) - is examined.
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.