{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:45:40Z","timestamp":1774946740028,"version":"3.50.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Docetaxel resistance is a major barrier to durable disease control in advanced and castration-resistant prostate cancer. There is a pharmacological need to identify biomarkers that not only stratify resistance risk but also nominate tractable regulators whose perturbation can restore taxane sensitivity and suppress resistant phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed docetaxel-resistant prostate cancer cell models to derive resistance-associated transcriptional candidates and used computational prioritization to construct a compact, taxane-resistance\u2013anchored gene set. Associations of the gene set and key candidates with disease progression were evaluated in TCGA-PRAD, which predominantly represents treatment-na\u00efve primary tumors and therefore provides progression relevance rather than treatment-specific response validation. Docetaxel-resistant cell lines were established for functional validation, and CRIP1 was stably silenced to assess effects on drug sensitivity, clonogenic growth, migration, apoptosis, and immune-associated cell-death features. In addition, an LNCaP-DTXr xenograft model was used to evaluate the impact of CRIP1 knockdown on docetaxel response\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A three-gene, taxane-resistance\u2013anchored signature was derived and showed progression-related associations in TCGA-PRAD. Among candidates, cysteine-rich protein 1 (CRIP1) was consistently upregulated in resistant models and emerged as a top resistance-associated factor. Functionally, CRIP1 knockdown restored docetaxel sensitivity, reduced clonogenic survival and migratory capacity, and enhanced docetaxel-induced apoptosis in resistant prostate cancer cells. Consistently, CRIP1 depletion significantly suppressed tumor growth and reduced tumor burden in docetaxel-treated LNCaP-DTXr xenografts, indicating restored chemosensitivity\n                      <jats:italic>in vivo<\/jats:italic>\n                      . In parallel, CRIP1 depletion was accompanied by changes in damage-associated and immune-related cell-death readouts under taxane stress, suggesting a potential role in linking drug tolerance to immune-relevant cell-death programs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify CRIP1 as a functionally validated, pharmacologically relevant mediator of docetaxel resistance in prostate cancer. While independent validation in taxane-treated clinical cohorts is warranted, our results support CRIP1 as a candidate therapeutic target and provide a mechanistic framework connecting taxane resistance with immune-associated cell-death modulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1769906","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:39:52Z","timestamp":1774942792000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CRIP1 promotes docetaxel resistance and immune-associated cell death modulation in prostate cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Dehua","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology, Yiling Hospital of Yichang, Affiliated Yiling Hospital of China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiling","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yiling Hospital of Yichang, Affiliated Yiling Hospital of China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ni","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Urology, Yiling Hospital of Yichang, Affiliated Yiling Hospital of China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Yiling Hospital of Yichang, Affiliated Yiling Hospital of China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Yiling Hospital of Yichang, Affiliated Yiling Hospital of China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology, Yiling Hospital of Yichang, Affiliated Yiling Hospital of China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxue","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Urology, Yiling Hospital of Yichang, Affiliated Yiling Hospital of China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Urology, Yiling Hospital of Yichang, Affiliated Yiling Hospital of China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1302811","DOI":"10.1155\/2021\/1302811","article-title":"Methods to analyze time-to-event data: the cox regression analysis","volume":"2021","author":"Abd ElHafeez","year":"2021","journal-title":"Oxid. 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