ArticleThe Prostate2020
Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens.
Article in The Prostate, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- MicroRNA profiles of prostate cancer bone metastases and miR-375 as an inhibitor of the aggressive metastasis subtype MetB.Scientific reports · 2026Article
- Kinesin Facilitates Phenotypic Targeting of Therapeutic Resistance in Advanced Prostate Cancer.Molecular cancer research : MCR · 2024Article
- Three-in-one: exploration of co-encapsulation of cabazitaxel, bicalutamide and chlorin e6 in new mixed cyclodextrin-crosslinked polymers.RSC advances · 2023Article
- Article
- Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p.Scientific reports · 2021Article
- Prediction of Synergistic Drug Combinations for Prostate Cancer by Transcriptomic and Network Characteristics.Frontiers in pharmacology · 2021Article
- Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens.The Prostate · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTaxane treatment may be a suitable therapeutic option for patients with castration-resistant prostate cancer and high expression of constitutively active androgen receptor variants (AR-Vs). The aim of the study was to compare the effects of cabazitaxel and androgen deprivation treatments in a prostate tumor xenograft model expressing high levels of constitutively active AR-V7. Furthermore, mechanisms behind acquired cabazitaxel resistance were explored.
methodsMice were subcutaneously inoculated with 22Rv1 cells and treated with surgical castration (n = 7), abiraterone (n = 9), cabazitaxel (n = 6), castration plus abiraterone (n = 8), castration plus cabazitaxel (n = 11), or vehicle and/or sham operation (n = 23). Tumor growth was followed for about 2 months or to a volume of approximately 1000 mm
resultsAbiraterone treatment alone or in combination with surgical castration had no major effect on 22Rv1 tumor growth, while cabazitaxel significantly delayed and in some cases totally abolished 22Rv1 tumor growth on its own and in combination with surgical castration. The cabazitaxel resistant cell lines; 22Rv1-CabR1 and 22Rv1-CabR2, both showed upregulation of the ATP-binding cassette sub-family B member 1 (ABCB1) efflux pump. Treatment with ABCB1 inhibitor elacridar completely restored susceptibility to cabazitaxel, while treatment with AR-antagonists bicalutamide and enzalutamide partly restored susceptibility to cabazitaxel in both cell lines. The cholesterol biosynthesis pathway was induced in the 22Rv1-CabR2 cell line, which was confirmed by reduced sensitivity to simvastatin treatment.
conclusionsCabazitaxel efficiently inhibits prostate cancer growth despite the high expression of constitutively active AR-V7. Acquired cabazitaxel resistance involving overexpression of efflux transporter ABCB1 can be reverted by bicalutamide or enzalutamide treatment, indicating the great clinical potential for combined treatment with cabazitaxel and anti-androgens.
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