Therapeutic Oligonucleotides Against Cancer: Recent Approaches and New Perspectives

Abstract The use of therapeutic oligonucleotides (TONs) has become a major alternative to treat disease thanks to recent advances in oligonucleotide synthesis and delivery technologies. Cancer is the result of progressive and accumulative changes in the cell genome and the host physiology that lead to uncontrolled growth and proliferation, metabolic changes, immune evasion, and ultimately metastasis and death. The present review focuses on oligonucleotide-based cancer therapies that have reached clinical trials. Although very effective in cell culture, TONs have faced severe delivery, pharmacokinetic, and stability issues. New conjugate, encapsulation, and formulation technologies improved the clinical application of TONs to treat cancer. Moreover, improvements in biostability and delivery have generated expectancies in cancer vaccine development, immunotherapy, and early detection. Therefore, the specificity, structural diversity, and versatility showed by TONs promise that they will become the treatment of choice for several types of cancer in the next few years.