Mechanism of cisplatin resistance in gastric cancer and associated microRNAs

Cancer Chemother Pharmacol. 2023 Nov;92(5):329-340. doi: 10.1007/s00280-023-04572-1. Epub 2023 Aug 3.

Abstract

Gastric cancer (GC) is a common malignant tumor with high morbidity and mortality rates that seriously affects human health worldwide. Although surgery is currently the preferred clinical treatment for GC, chemotherapy remains the first choice for perioperative treatment, adjuvant therapy, and palliative care for patients with advanced GC. Cisplatin (DDP) is an antineoplastic agent that has been used clinically for decades, and it is the first-line chemotherapy for many solid tumors. However, the therapeutic efficacy of DDP is often limited by resistance and the complexity of its resistance mechanisms, which involve multiple proteins and signaling pathways. It is well documented that a variety of microRNAs (miRNAs) differentially expressed in DDP-resistant GC cells play important roles in regulating or reversing DDP resistance via various pathways. In this review, we first provide an introduction to the cytotoxicity and major resistance mechanisms of DDP in GC and then discuss the role and mechanism of miRNAs in regulating the DDP resistance process in GC cells. This work demonstrates the potential of relevant miRNAs to become diagnostic and prognostic biomarkers for gastric cancer and targets of action to enhance chemosensitivity and provides directions for future research.

Keywords: Cancer multidrug resistance; Cisplatin resistance; Gastric cancer; Gene regulation; MicroRNAs; Therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology

Substances

  • Cisplatin
  • MicroRNAs
  • Antineoplastic Agents