Advances in RNAi therapies for gastric cancer: Targeting drug resistance and nanoscale delivery

Biomed Pharmacother. 2023 Dec 31:169:115927. doi: 10.1016/j.biopha.2023.115927. Epub 2023 Nov 24.

Abstract

Gastric cancer poses a significant health challenge, and exploring innovative therapeutic strategies is imperative. RNA interference (RNAi) has employed as an important therapeutic strategy for diseases by selectively targeting key pathways involved in diseases pathogenesis. Small interfering RNA (siRNA), a potent RNAi tool, possesses the capability to silence genes and downregulate their expression. This review provides a comprehensive examination of the potential applications of small interfering RNA (siRNA) and short hairpin RNA (shRNA), supplemented by an in-depth analysis of nanoscale delivery systems, in the context of gastric cancer treatment. The potential of siRNA to markedly diminish the proliferation and invasion of gastric cancer cells through the modulation of critical molecular pathways, including PI3K, Akt, and EMT, is highlighted. Besides, siRNA demonstrates its efficacy in inducing chemosensitivity in gastric tumor cells, thus impeding tumor progression. However, the translational potential of unmodified siRNA faces challenges, particularly in vivo and during clinical trials. To address this, we underscore the pivotal role of nanostructures in facilitating the delivery of siRNA to gastric cancer cells, effectively suppressing their progression and enhancing gene silencing efficiency. These siRNA-loaded nanoparticles exhibit robust internalization into gastric cancer cells, showcasing their potential to significantly reduce tumor progression. The translation of these findings into clinical trials holds promise for advancing the treatment of gastric cancer patients.

Keywords: Cancer therapy; Gastric cancer; Gene delivery; Nanoparticles; SiRNA.

Publication types

  • Review

MeSH terms

  • Drug Delivery Systems
  • Drug Resistance
  • Humans
  • Nanoparticles* / chemistry
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNAi Therapeutics
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / therapy

Substances

  • RNA, Small Interfering