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<p>Chemoresistance remains a major barrier to durable disease control in gastric cancer, limiting the effectiveness of perioperative and palliative systemic therapies. Increasing evidence indicates that resistance is driven by a complex interplay between tumor-intrinsic adaptations and tumor microenvironment-mediated survival pathways. Although chemoresistance can be innate or acquired, a variety of mechanisms could coexist within the tumor, with various processes acting synergistically. MicroRNAs, as key post-transcriptional regulators, have emerged as central modulators of these resistance networks. This review summarizes the principal mechanisms of chemoresistance in gastric cancer and synthesizes current evidence on how microRNAs—derived from tumor cells and the tumor microenvironment—promote or reverse resistance to commonly used chemotherapeutic agents and targeted therapy/immunotherapies, highlighting therapeutic opportunities. Evidence was organized by mechanism (drug transport and metabolism, DNA damage response, apoptosis and survival signaling, autophagy, epithelial-to-mesenchymal transition/cancer stem cell plasticity, and immune escape) and by drug class.</p>

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Mechanisms of chemoresistance in gastric cancer: interplay between microRNAs and the tumor microenvironment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月6日

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  • Vlad-Costin Ilie,
  • Corina-Elena Minciuna,
  • Catalin Andras,
  • Simona Nicoleta Turcu,
  • Vlad Herlea,
  • Simona Olimpia Dima,
  • Gabriela Droc,
  • Monica Lacatus,
  • Stefan Tudor,
  • Catalin Vasilescu

摘要

Chemoresistance remains a major barrier to durable disease control in gastric cancer, limiting the effectiveness of perioperative and palliative systemic therapies. Increasing evidence indicates that resistance is driven by a complex interplay between tumor-intrinsic adaptations and tumor microenvironment-mediated survival pathways. Although chemoresistance can be innate or acquired, a variety of mechanisms could coexist within the tumor, with various processes acting synergistically. MicroRNAs, as key post-transcriptional regulators, have emerged as central modulators of these resistance networks. This review summarizes the principal mechanisms of chemoresistance in gastric cancer and synthesizes current evidence on how microRNAs—derived from tumor cells and the tumor microenvironment—promote or reverse resistance to commonly used chemotherapeutic agents and targeted therapy/immunotherapies, highlighting therapeutic opportunities. Evidence was organized by mechanism (drug transport and metabolism, DNA damage response, apoptosis and survival signaling, autophagy, epithelial-to-mesenchymal transition/cancer stem cell plasticity, and immune escape) and by drug class.