Pancreatic cancer and oligonucleotide therapy: Exploring novel therapeutic options and targeting chemoresistance

Clin Res Hepatol Gastroenterol. 2022 May;46(5):101911. doi: 10.1016/j.clinre.2022.101911. Epub 2022 Mar 25.

Abstract

Pancreatic cancer (PC) represents a malignancy with increased mortality rate, as less than 10% of patients survive for 5 years after diagnosis. Current evolution in basic sciences has revealed promising results by decrypting genetic loci vulnerable to mutations, as potential targets of novel treatment choices. In this regard, the "Oligonucleotide therapeutics", based on synthetic nucleotides, modify the function and expression of their targets. Antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNAs (miRNAs), aptamers, CpG oligodeoxynucleotides and decoys comprise the main representatives of this emerging technology, by regulating oncogenes' expression, restoring DNA repairment mechanisms, sensitizing cancer cells in chemotherapy, and inhibiting PC progress. A plethora of genetic treatment molecules and respective targets have been described and are currently studied, thus providing a broad range of probable pharmaceutical options. This narrative review illuminates the main parameters of genetic treatment molecules for PC and underlines their deficiencies, to clarify the upcoming future and trigger further investigation in PC management.

Keywords: Chemoresistance; Gene therapy; Oligonucleotide treatment; Oncogene; Pancreatic cancer; RNAi; miRNA.

Publication types

  • Review

MeSH terms

  • Drug Resistance, Neoplasm / genetics
  • Humans
  • MicroRNAs* / genetics
  • Oligonucleotides / therapeutic use
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / therapeutic use

Substances

  • MicroRNAs
  • Oligonucleotides
  • Oligonucleotides, Antisense
  • RNA, Small Interfering