Abstract
Approximately 30% of pancreatic cancer patients harbor targetable mutations. However, there has been no therapy targeting these molecules clinically. Nucleic acid medicines show high specificity and can target RNAs. Nucleic acid medicine is expected to be the next-generation treatment next to small molecules and antibodies. There are several kinds of nucleic acid drugs, including antisense oligonucleotides, small interfering RNAs, microRNAs, aptamers, decoys, and CpG oligodeoxynucleotides. In this review, we provide an update on current research of nucleic acid-based therapies. Despite the challenging obstacles, we hope that nucleic acid drugs will have a significant impact on the treatment of pancreatic cancer. The combination of genetic diagnosis using next generation sequencing and targeted therapy may provide effective precision medicine for pancreatic cancer patients.
Highlights
Despite advances in diagnostics and therapeutics, the prognosis of pancreatic cancer remains poor with an overall five-year survival rate of 6%, due in part to difficulties in treating carcinoma at an advanced stage
There are several kinds of nucleic acid drugs, including antisense oligonucleotides (ASOs), small interfering RNAs, microRNAs, aptamers, decoys, and CpG oligodeoxynucleotides (CpG oligos) (Table 1). They can be classified as either extracellular or intracellular according to their site of function; ASOs, siRNAs, miRNAs, and decoys act in the nucleus or cytoplasm, while aptamers bind to extracellular proteins and CpG oligos act on Toll-like receptor 9 (TLR9) in the endosome
We provide an update on the current research of nucleic acid-based therapies, focusing on ASO and siRNA for pancreatic cancer, and summarize the outcomes from published data
Summary
Despite advances in diagnostics and therapeutics, the prognosis of pancreatic cancer remains poor with an overall five-year survival rate of 6%, due in part to difficulties in treating carcinoma at an advanced stage. Nucleic acid medicine consists of natural or chemically modified nucleotides that can act directly without changes in gene expression [3] These drugs show high specificity and can target mRNA and noncoding RNAs. Nucleic acid medicine is considered the next-generation treatment next to small molecules and antibodies. There are several kinds of nucleic acid drugs, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamers, decoys, and CpG oligodeoxynucleotides (CpG oligos) (Table 1) They can be classified as either extracellular or intracellular according to their site of function; ASOs, siRNAs, miRNAs, and decoys act in the nucleus or cytoplasm, while aptamers bind to extracellular proteins and CpG oligos act on Toll-like receptor 9 (TLR9) in the endosome.
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