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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\u2014derived from tumor cells and the tumor microenvironment\u2014promote 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.<\/jats:p>","DOI":"10.1007\/s12094-026-04377-7","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T14:47:00Z","timestamp":1778078820000},"page":"4328-4345","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms of chemoresistance in gastric cancer: interplay between microRNAs and the tumor microenvironment"],"prefix":"10.1007","volume":"28","author":[{"given":"Vlad-Costin","family":"Ilie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4074-8967","authenticated-orcid":false,"given":"Corina-Elena","family":"Minciuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin","family":"Andras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Nicoleta","family":"Turcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Herlea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Olimpia","family":"Dima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Droc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Lacatus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Tudor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin","family":"Vasilescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"4377_CR1","unstructured":"Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Pi\u00f1eros M, Znaor A, Soerjomataram I, Bray F. 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