Androgen receptor signalling impairs docetaxel efficacy in castration-resistant prostate cancer

Lisanne Mout, Matthijs Moll, M Chen, Ellen Morrée, Corrina de Ridder, A Gibson, Debra Stuurman, Ashraf Jozefzoon - Aghai, Sigrun Erkens - Schulze, Ron Mathijssen, A Sparreboom, Ronald de Wit, Martijn Lolkema, Wytske van Weerden*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)
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Androgen receptor (AR) signalling drives neoplastic growth and therapy resistance in prostate cancer. Recent clinical data show that docetaxel combined with androgen deprivation therapy improves outcome in hormone-sensitive disease. We studied whether testosterone and AR signalling interferes with docetaxel treatment efficacy in castration-resistant prostate cancer (CRPC). We found that testosterone supplementation significantly impaired docetaxel tumour accumulation in a CRPC model, resulting in decreased tubulin stabilisation and antitumour activity. Furthermore, testosterone competed with docetaxel for uptake by the drug transporter OATP1B3. Irrespective of docetaxel-induced tubulin stabilisation, AR signalling by testosterone counteracted docetaxel efficacy. AR-pathway activation could also reverse long-term tumour regression by docetaxel treatment in vivo. These results indicate that to optimise docetaxel efficacy, androgen levels and AR signalling need to be suppressed. This study lends evidence for continued maximum suppression of AR signalling by combining targeted therapeutics with docetaxel in CRPC.

Original languageEnglish
Pages (from-to)1715-1719
Number of pages5
JournalBritish Journal of Cancer
Issue number12
Publication statusPublished - 8 Dec 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Cancer Research UK.


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