Insights into Chemoresistance of Prostate Cancer

Int J Biol Sci. 2015 Aug 1;11(10):1160-70. doi: 10.7150/ijbs.11439. eCollection 2015.

Abstract

Prostate cancer (PCa) remains the most prevalent malignancy among males in the western world. Though hormonal therapies through chemical or surgical castration have been proposed many years ago, heretofore, such mainstay for the treatment on advanced PCa has not fundamentally changed. These therapeutic responses are temporary and most cases will eventually undergo PCa recurrence and metastasis, or even progress to castration-resistant prostate cancer (CRPC) due to persistent development of drug resistance. Prostate cancer stem cells (PCSCs) are a small population of cells, which possess unlimited self-renewal capacities, and can regenerate tumorigenic progenies, and play an essential role in PCa therapy resistance, metastasis and recurrence. Nowadays advanced progresses have been made in understanding of PCSC properties, roles of androgen receptor signaling and ATP-binding cassette sub-family G member 2 (ABCG2), as well as roles of genomic non-coding microRNAs and key signaling pathways, which have led to the development of novel therapies which are active against chemoresistant PCa and CRPC. Based on these progresses, this review is dedicated to address mechanisms underlying PCa chemoresistance, unveil crosstalks among pivotal signaling pathways, explore novel biotherapeutic agents, and elaborate functional properties and specific roles of chemoresistant PCSCs, which may act as a promising target for novel therapies against chemoresistant PCa.

Keywords: androgen receptor; cancer recurrence; cancer stem cell; chemoresistance; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism*
  • Bridged-Ring Compounds
  • Drug Resistance, Neoplasm*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / metabolism*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Taxoids

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Bridged-Ring Compounds
  • MicroRNAs
  • Neoplasm Proteins
  • Receptors, Androgen
  • Taxoids
  • taxane