Related Experiment Video

Updated: Sep 7, 2025

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

13.5K

Itraconazole Reverts ABCB1-Mediated Docetaxel Resistance in Prostate Cancer

Thiago S Lima1,2, Luciano O Souza1,3, Diego Iglesias-Gato1

  • 1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Frontiers in Pharmacology
|June 20, 2022
PubMed

Insights

Itraconazole (ITZ), an antifungal drug, can re-sensitize docetaxel-resistant prostate cancer cells to docetaxel (DTX) treatment. This effect is mediated by ITZ inhibiting the P-glycoprotein transporter, offering a potential strategy to overcome drug resistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) shows limited response to docetaxel (DTX).
  • Drug resistance, often mediated by ABC transporter proteins like P-glycoprotein (P-gp), limits DTX efficacy.
  • Novel strategies are needed to overcome DTX resistance in prostate cancer.

Purpose of the Study:

  • To identify compounds that can re-sensitize DTX-resistant prostate cancer cells to DTX.
  • To investigate the mechanism by which identified compounds overcome DTX resistance.

Main Methods:

  • Established and utilized DTX-resistant prostate cancer cell lines (LNCaPR, C4-2BR).
  • Conducted an unbiased drug screen to identify re-sensitizing agents.
  • Investigated the role of ABCB1 (P-gp) expression and function.
  • Performed molecular modeling of itraconazole (ITZ) bound to ABCB1.

Main Results:

  • Identified itraconazole (ITZ), an antifungal drug, as a potent re-sensitizer of DTX-resistant prostate and breast cancer cells.
  • Demonstrated that ITZ's re-sensitizing effect is dependent on ABCB1 (P-gp) expression.
  • Molecular modeling revealed ITZ binds to ABCB1, inhibiting DTX transport.

Conclusions:

  • Itraconazole (ITZ) effectively re-sensitizes docetaxel-resistant cancer cells by inhibiting P-glycoprotein (P-gp).
  • ITZ represents a promising therapeutic strategy to overcome DTX resistance in metastatic castration-resistant prostate cancer.
  • This approach may enhance the efficacy and duration of DTX treatment in patients.
Keywords:
androgen independencecellular modelsdocetaxel resistancedrug repurposingmetastatic castration-resistant prostate cancer

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