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Bumbaca B, Li W. Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies. Acta Pharm Sin B. 2018;8(4):518-529doi: 10.1016/j.apsb.2018.04.007.
Bumbaca, B., & Li, W. (2018). Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies. Acta pharmaceutica Sinica. B, 8(4), 518-529. https://doi.org/10.1016/j.apsb.2018.04.007
Bumbaca, Brandon, and Li, Wei. "Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies." Acta pharmaceutica Sinica. B vol. 8,4 (2018): 518-529. doi: https://doi.org/10.1016/j.apsb.2018.04.007
Bumbaca B, Li W. Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies. Acta Pharm Sin B. 2018 Jul;8(4):518-529. doi: 10.1016/j.apsb.2018.04.007. Epub 2018 Apr 30. PMID: 30109177; PMCID: PMC6089846.
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Acta Pharm Sin B. 2018 Jul;8(4):518-529. doi: 10.1016/j.apsb.2018.04.007. Epub 2018 Apr 30.

Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies.

Acta pharmaceutica Sinica. B

Brandon Bumbaca, Wei Li

Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, the University of Tennessee Health Science Center, Memphis, TN 38163, USA.

PMID: 30109177 PMCID: PMC6089846 DOI: 10.1016/j.apsb.2018.04.007

Abstract

Despite its good initial response and significant survival benefit in patients with castration-resistant prostate cancer (CRPC), taxane therapy inevitably encounters drug resistance in all patients. Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression, and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics, indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.

Keywords: Androgen receptor; Cancer stem cells; Castration-resistant prostate cancer; Drug efflux transporters; Efflux transporter; Microtubules; PI3K/AKT pathway; Taxane resistance

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