Taxane resistance in castration-resistant prostate cancer

mechanisms and therapeutic strategies

Brandon Bumbaca, Wei Li

Research output: Contribution to journalReview article

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)518-529
Number of pages12
JournalActa Pharmaceutica Sinica B
Volume8
Issue number4
DOIs
StatePublished - Jul 1 2018

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Castration
Prostatic Neoplasms
Up-Regulation
Therapeutics
Taxoids
Survival
Androgen Receptors
Tubulin
Drug Resistance
Microtubules
taxane
Neoplasms
Stem Cells
Binding Sites
Mutation

All Science Journal Classification (ASJC) codes

  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Taxane resistance in castration-resistant prostate cancer : mechanisms and therapeutic strategies. / Bumbaca, Brandon; Li, Wei.

In: Acta Pharmaceutica Sinica B, Vol. 8, No. 4, 01.07.2018, p. 518-529.

Research output: Contribution to journalReview article

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