{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:05:46Z","timestamp":1789635946736,"version":"4.0.0"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023MH029"],"award-info":[{"award-number":["ZR2023MH029"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Fibroblast growth factor receptor (FGFR) signaling is a major oncogenic pathway in multiple cancer types and an important determinant of therapeutic response and resistance. However, its role in coordinating apoptotic susceptibility with tumor immune escape remains insufficiently integrated. This review summarizes how FGFR signaling regulates mitochondrial apoptosis through the RAS\u2013RAF\u2013MEK\u2013ERK, PI3K\u2013AKT\u2013mTOR, PLC\u03b3\u2013PKC\/Ca\u00b2\n                    <jats:sup>+<\/jats:sup>\n                    , and JAK\u2013STAT pathways. These signaling networks converge on BCL-2 family proteins, BH3-only regulators, FOXO-dependent transcription, BAX\/BAK activation, mitochondrial outer membrane permeabilization, cytochrome c release, and caspase activation. Non-canonical mechanisms involving redox homeostasis, metabolic stress, c-Myc regulation, and autophagy further determine whether FGFR inhibition produces transient adaptation or irreversible cell death. FGFR alterations may also shape the immune contexture of selected tumors by influencing inflammatory signaling, PD-L1 regulation, antigen-presentation pathways, tumor\u2013stromal interactions, and susceptibility to immune-mediated elimination. These effects are strongly dependent on tumor lineage, genomic background, bypass receptor tyrosine kinase signaling, mitochondrial priming, and the local immune microenvironment. We further synthesize preclinical and emerging clinical evidence for combining FGFR-targeted therapies with immune checkpoint blockade and discuss the biomarkers and limitations that may determine therapeutic benefit. By linking apoptotic regulation, immune evasion, and therapeutic resistance, this review provides a framework for mechanism-based treatment strategies in FGFR-aberrant cancers.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1953431","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:37:42Z","timestamp":1789634262000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["FGFR signaling and apoptotic regulation in cancer: links to immune evasion, therapeutic resistance, and treatment re-engagement"],"prefix":"10.3389","volume":"17","author":[{"given":"Yinan","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pathology, The 960th Hospital of the People\u2019s Liberation Army (PLA) Joint Logistic Support Force","place":["Jinan, China"]},{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 960th Hospital of the People\u2019s Liberation Army (PLA) Joint Logistic Support Force","place":["Jinan, China"]},{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 960th Hospital of the People\u2019s Liberation Army (PLA) Joint Logistic Support Force","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 960th Hospital of the People\u2019s Liberation Army (PLA) Joint Logistic Support Force","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 960th Hospital of the People\u2019s Liberation Army (PLA) Joint Logistic Support Force","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 960th Hospital of the People\u2019s Liberation Army (PLA) Joint Logistic Support Force","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, The 960th Hospital of the People\u2019s Liberation Army (PLA) Joint Logistic Support Force","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peifeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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