Non-coding RNAs in gastric cancer: mechanisms and therapeutic prospects

Mol Cancer. 2025 Oct 3;24(1):244. doi: 10.1186/s12943-025-02467-8.

Abstract

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. It is associated with high molecular and phenotypic heterogeneity. Early-stage gastric cancer can be treated with endoscopic resection and surgery, whereas at its advanced stage, sequential chemotherapy presents the only treatment option, which starts with first-line platinum and fluoropyrimidine-based dual drugs, supporting a median survival period of less than one year. Targeted monoclonal antibodies approved for the treatment of gastric cancer are effective for a limited subset of patients. Furthermore, painless and precise markers for the early detection of gastric cancer and new targets for its treatment are unavailable. Interestingly, many non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play key roles in the development of gastric cancer. Multiple pieces of evidence suggest that ncRNAs play a crucial role in the treatment of gastric cancer using chemotherapy and targeted therapy drugs. In this article, we systematically reviewed the important roles of ncRNAs in chemotherapy resistance, immune escape, metabolism, and angiogenesis of gastric cancer, and systematically elucidated the relevant molecular mechanisms. In addition, we also proposed the potential clinical significance of ncRNA as a new therapeutic target and prognostic biomarker for gastric cancer.

Keywords: Biomarker; Chemotherapy; Drug resistance; Gastric cancer; Non-coding RNAs.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor* / genetics
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Prognosis
  • RNA, Circular / genetics
  • RNA, Untranslated* / genetics
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / therapy

Substances

  • Biomarkers, Tumor
  • RNA, Untranslated
  • RNA, Circular