Antisense Therapy in Clinical Oncology: Preclinical and Clinical Experiences

Nucleic acid molecules have emerged as versatile tools with promising utility as therapeutics for human diseases. The specificity of hybridization of an antisense oligonucleotide (AS-ODN) to the target mRNA makes the antisense strategy attractive for selectively modulating the expression of genes involved in the pathogenesis of malignant or nonmalignant diseases. One antisense drug has been approved for local therapy of cytomegalovirus (CMV) retinitis, and a number of AS-ODNs are currently being tested in clinical trials including oglionucelotides that target bcl-2, protein kinase C-α (PKC-α), and DNA methyltransferase. Clinical studies indicate that AS-ODNs are well tolerated and may have therapeutic activity. In this overview, we summarize therapeutic concepts, clinical studies, and new promising molecular targets to treat human cancer with AS-ODNs.