ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
This article is part of the Research TopicAdvances in Biomarkers and Drug Targets: Harnessing Traditional and AI Approaches for Novel Therapeutic MechanismsView all 21 articles
CRIP1 promotes docetaxel resistance and immune-associated cell death modulation in prostate cancer
Provisionally accepted
- Yiling People's Hospital, Yichang, China
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Background: 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. Methods: We analyzed docetaxel-resistant prostate cancer cell models to derive resistance-associated transcriptional candidates and used computational prioritization to construct a compact, taxane-resistance–anchored gene set. Associations of the gene set and key candidates with disease progression were evaluated in TCGA-PRAD, which predominantly represents treatment-naïve 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 in vivo. Results: A three-gene, taxane-resistance–anchored 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 in vivo. 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. Conclusion: 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.
Keywords: chemotherapy resistance, Computational prioritization, Crip1, Docetaxel resistance, drug target, Immunogenic cell death, prostate cancer
Received: 17 Dec 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 zhang, Han, Yan, Zhang, Wang, Shi, Jia and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jun Gao
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