Collateral resistance to taxanes in enzalutamide-resistant prostate cancer through aberrant androgen receptor and its variants

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Currently, the optimal sequential use of androgen receptor (AR) axis-targeted agents and taxane chemotherapies remains undetermined. We aimed to elucidate the resistance status between taxanes and enzalutamide, and the functional role of the AR axis. Enzalutamide-resistant 22Rv1 cells showed collateral resistance to taxanes, including docetaxel and cabazitaxel. However, taxane-resistant cells showed no collateral resistance to enzalutamide; taxane-resistant cells expressed comparable protein levels of full-length AR and AR variants. Knockdown of both full-length AR and AR variants rendered cells sensitive to taxanes, whereas knockdown of AR variants sensitized cells to enzalutamide, but not to taxanes. In contrast, overexpression of full-length AR rendered cells resistant to taxanes. Consistently, the prostate-specific antigen response and progression-free survival in docetaxel chemotherapy were worse in cases with prior use of ARAT agents compared with cases without. Collateral resistance to taxanes was evident after obtaining enzalutamide resistance, and aberrant AR signaling might be involved in taxane resistance.

元の言語英語
ページ(範囲)3224-3234
ページ数11
ジャーナルCancer Science
109
発行部数10
DOI
出版物ステータス出版済み - 10 1 2018

Fingerprint

Taxoids
Androgen Receptors
Prostatic Neoplasms
docetaxel
MDV 3100
Drug Therapy
Prostate-Specific Antigen
Disease-Free Survival
taxane

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

@article{54a630d3d2594e4094e3f7d32f5b86d1,
title = "Collateral resistance to taxanes in enzalutamide-resistant prostate cancer through aberrant androgen receptor and its variants",
abstract = "Currently, the optimal sequential use of androgen receptor (AR) axis-targeted agents and taxane chemotherapies remains undetermined. We aimed to elucidate the resistance status between taxanes and enzalutamide, and the functional role of the AR axis. Enzalutamide-resistant 22Rv1 cells showed collateral resistance to taxanes, including docetaxel and cabazitaxel. However, taxane-resistant cells showed no collateral resistance to enzalutamide; taxane-resistant cells expressed comparable protein levels of full-length AR and AR variants. Knockdown of both full-length AR and AR variants rendered cells sensitive to taxanes, whereas knockdown of AR variants sensitized cells to enzalutamide, but not to taxanes. In contrast, overexpression of full-length AR rendered cells resistant to taxanes. Consistently, the prostate-specific antigen response and progression-free survival in docetaxel chemotherapy were worse in cases with prior use of ARAT agents compared with cases without. Collateral resistance to taxanes was evident after obtaining enzalutamide resistance, and aberrant AR signaling might be involved in taxane resistance.",
author = "masaki shiota and Takashi Dejima and Yoshiaki Yamamoto and ario takeuchi and Kenjiro Imada and Eiji Kashiwagi and Junichi Inokuchi and Katsunori Tatsugami and Shunichi Kajioka and Takeshi Uchiumi and Masatoshi Eto",
year = "2018",
month = "10",
day = "1",
doi = "10.1111/cas.13751",
language = "English",
volume = "109",
pages = "3224--3234",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Collateral resistance to taxanes in enzalutamide-resistant prostate cancer through aberrant androgen receptor and its variants

AU - shiota, masaki

AU - Dejima, Takashi

AU - Yamamoto, Yoshiaki

AU - takeuchi, ario

AU - Imada, Kenjiro

AU - Kashiwagi, Eiji

AU - Inokuchi, Junichi

AU - Tatsugami, Katsunori

AU - Kajioka, Shunichi

AU - Uchiumi, Takeshi

AU - Eto, Masatoshi

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Currently, the optimal sequential use of androgen receptor (AR) axis-targeted agents and taxane chemotherapies remains undetermined. We aimed to elucidate the resistance status between taxanes and enzalutamide, and the functional role of the AR axis. Enzalutamide-resistant 22Rv1 cells showed collateral resistance to taxanes, including docetaxel and cabazitaxel. However, taxane-resistant cells showed no collateral resistance to enzalutamide; taxane-resistant cells expressed comparable protein levels of full-length AR and AR variants. Knockdown of both full-length AR and AR variants rendered cells sensitive to taxanes, whereas knockdown of AR variants sensitized cells to enzalutamide, but not to taxanes. In contrast, overexpression of full-length AR rendered cells resistant to taxanes. Consistently, the prostate-specific antigen response and progression-free survival in docetaxel chemotherapy were worse in cases with prior use of ARAT agents compared with cases without. Collateral resistance to taxanes was evident after obtaining enzalutamide resistance, and aberrant AR signaling might be involved in taxane resistance.

AB - Currently, the optimal sequential use of androgen receptor (AR) axis-targeted agents and taxane chemotherapies remains undetermined. We aimed to elucidate the resistance status between taxanes and enzalutamide, and the functional role of the AR axis. Enzalutamide-resistant 22Rv1 cells showed collateral resistance to taxanes, including docetaxel and cabazitaxel. However, taxane-resistant cells showed no collateral resistance to enzalutamide; taxane-resistant cells expressed comparable protein levels of full-length AR and AR variants. Knockdown of both full-length AR and AR variants rendered cells sensitive to taxanes, whereas knockdown of AR variants sensitized cells to enzalutamide, but not to taxanes. In contrast, overexpression of full-length AR rendered cells resistant to taxanes. Consistently, the prostate-specific antigen response and progression-free survival in docetaxel chemotherapy were worse in cases with prior use of ARAT agents compared with cases without. Collateral resistance to taxanes was evident after obtaining enzalutamide resistance, and aberrant AR signaling might be involved in taxane resistance.

UR - http://www.scopus.com/inward/record.url?scp=85052793434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052793434&partnerID=8YFLogxK

U2 - 10.1111/cas.13751

DO - 10.1111/cas.13751

M3 - Article

VL - 109

SP - 3224

EP - 3234

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 10

ER -