{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:36:55Z","timestamp":1787841415498,"version":"build-2784847793"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Transformed small-cell lung cancer (T-SCLC) is a clinically important form of histologic transformation and a mechanism of acquired resistance in non-small-cell lung cancer (NSCLC). It is associated with poor prognosis, with a median overall survival of only about 9\u201313\u202fmonths. This review summarizes recent advances in the mechanisms, diagnosis, monitoring, and treatment of T-SCLC. Repeat biopsy remains the gold standard for confirming histologic transformation, whereas molecular profiling and liquid biopsy may facilitate early detection and longitudinal disease monitoring. Platinum-etoposide remains the most commonly used clinical standard after transformation, but its benefit is typically transient and durable disease control remains uncommon. Continuation of\n                    <jats:italic>EGFR<\/jats:italic>\n                    tyrosine kinase inhibitors combined with chemotherapy may prolong progression-free survival in selected patients but has not consistently improved overall survival. Anti-angiogenic therapy, particularly anlotinib, and chemo-immunotherapy have shown encouraging activity in selected patients, while emerging strategies targeting\n                    <jats:italic>DLL3<\/jats:italic>\n                    ,\n                    <jats:italic>MYC<\/jats:italic>\n                    ,\n                    <jats:italic>SOX2<\/jats:italic>\n                    , and epigenetic regulators may broaden the therapeutic landscape. Prospective studies integrating repeat tissue sampling, comprehensive genomic profiling, biomarker-guided patient stratification, pharmacogenomics, functional drug-sensitivity testing where feasible, and integrated multi-omics approaches are needed to advance molecularly guided and individualized treatment for T-SCLC.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1865050","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:54:03Z","timestamp":1787838843000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Advanced and underlying therapeutic strategies in transformed small cell lung cancer"],"prefix":"10.3389","volume":"13","author":[{"given":"Mingfeng","family":"Wei","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Clinical Geriatric Medicine, Affiliated Huadong Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Clinical Geriatric Medicine, Affiliated Huadong Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Clinical Geriatric Medicine, Affiliated Huadong Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixiang","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Clinical Geriatric Medicine, Affiliated Huadong Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lefei","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Clinical Geriatric Medicine, Affiliated Huadong Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzhi","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Clinical Geriatric Medicine, Affiliated Huadong Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Clinical Geriatric Medicine, Affiliated Huadong Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Clinical Geriatric Medicine, Affiliated Huadong Hospital, Fudan University","place":["Shanghai, 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