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Oncol."],"abstract":"<jats:p>Paclitaxel is a cornerstone microtubule-stabilizing agent, but intrinsic and acquired resistance limit durable benefit. Resistance emerges from interacting changes in drug transport, tubulin composition, microtubule regulation, mitotic fate, apoptosis, autophagy, cellular plasticity and the tumor microenvironment. The stathmin family\u2014STMN1, STMN2, STMN3 and STMN4\u2014controls microtubule assembly through tubulin sequestration and catastrophe-promoting activity and therefore occupies a direct functional interface with paclitaxel pharmacodynamics. STMN1 has the strongest evidence: overexpression can reduce taxane sensitivity, whereas suppression restores microtubule stabilization and drug response in several experimental systems; clinical studies also associate high STMN1 with unfavorable outcome or reduced taxane benefit in selected cancers. Evidence for STMN3 is narrower but includes a mechanistically relevant ovarian-cancer study in which bisphosphorylated PEA-15 sensitized cells to paclitaxel by attenuating SCLIP\/STMN3-mediated microtubule destabilization. By contrast, direct evidence for STMN2 and STMN4 in taxane response remains insufficient. This review develops a microtubule-centered resistance model, distinguishes established findings from context-dependent observations and testable hypotheses, and evaluates biomarker and therapeutic strategies targeting stathmin expression, phosphorylation, stability and protein interactions. We propose that stathmin activity is most likely to have clinical value as part of a composite taxane-response classifier that also incorporates intracellular drug exposure, tubulin isotypes and apoptotic competence.<\/jats:p>","DOI":"10.3389\/fonc.2026.1940719","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:48:23Z","timestamp":1788263303000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond STMN1: stathmin-family control of microtubule dynamics and paclitaxel resistance in cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Haoyu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Kunshan First People\u2019s Hospital Affiliated to Jiangsu University","place":["Kunshan, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhou","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Kunshan Women and Children\u2019s Healthcare Hospital","place":["Kunshan, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kunshan First People\u2019s Hospital Affiliated to Jiangsu University","place":["Kunshan, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Kunshan Women and Children\u2019s Healthcare Hospital","place":["Kunshan, Jiangsu, China"]},{"name":"Department of General Surgery, Kunshan First People\u2019s Hospital Affiliated to Jiangsu University","place":["Kunshan, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1317","article-title":"Microtubules as a target for anticancer drugs","volume":"4","author":"Jordan","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113323","article-title":"Mechanisms of taxane resistance","volume":"12","author":"Maloney","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100742","article-title":"Taxanes in cancer treatment: Activity, chemoresistance and its overcoming","volume":"54","author":"Mosca","year":"2021","journal-title":"Drug Resist Update"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2021.100754","article-title":"Therapeutic strategies to overcome taxane resistance in cancer","volume":"55","author":"Das","year":"2021","journal-title":"Drug Resist Update"},{"key":"B5","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s12935-024-03415-0","article-title":"Key genes and molecular mechanisms related to Paclitaxel Resistance","volume":"24","author":"Alalawy","year":"2024","journal-title":"Cancer Cell Int"},{"key":"B6","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.bbcan.2007.10.004","article-title":"Taxanes, microtubules and chemoresistant breast cancer","volume":"1785","author":"McGrogan","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"B7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12967-016-1000-z","article-title":"Stathmin-dependent molecular targeting therapy for Malignant tumor: the latest 5 years discoveries and developments","volume":"14","author":"Rong","year":"2016","journal-title":"J Transl Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S1499-3872(14)60038-2","article-title":"Stathmin destabilizing microtubule dynamics promotes Malignant potential in cancer cells by epithelial-mesenchymal transition","volume":"13","author":"Lu","year":"2014","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2011.620951","article-title":"Stathmin: a protein with many tasks. 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