Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer

被引：1128

作者：

Watson, Philip A. ^{[1
]}

Arora, Vivek K. ^{[2
]}

Sawyers, Charles L. ^{[1
,3
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[2] Washington Univ, Sch Med, Div Med Oncol, St Louis, MO 63130 USA

[3] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

NATURE REVIEWS CANCER | 2015年 / 15卷 / 12期

基金：

美国国家卫生研究院;

关键词：

SMALL-CELL CARCINOMA; BRCA MUTATION CARRIERS; ABIRATERONE ACETATE; SPLICE VARIANTS; POLY(ADP-RIBOSE) POLYMERASE; PROGESTERONE-RECEPTOR; WITHDRAWAL SYNDROME; ANTITUMOR-ACTIVITY; MOLECULAR CHARACTERIZATION; SELECTIVE-INHIBITION;

D O I：

10.1038/nrc4016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

During the past 10 years, preclinical studies implicating sustained androgen receptor (AR) signalling as the primary driver of castration-resistant prostate cancer (CRPC) have led to the development of novel agents targeting the AR pathway that are now in widespread clinical use. These drugs prolong the survival of patients with late-stage prostate cancer but are not curative. In this Review, we highlight emerging mechanisms of acquired resistance to these contemporary therapies, which fall into the three broad categories of restored AR signalling, AR bypass signalling and complete AR independence. This diverse range of resistance mechanisms presents new challenges for long-term disease control, which may be addressable through early use of combination therapies guided by recent insights from genomic landscape studies of CRPC.

引用

页码：701 / 711

页数：11

共 148 条

[1] AKR1C3 as a target in castrate resistant prostate cancer [J].

Adeniji, Adegoke O. ;

Chen, Mo ;

Penning, Trevor M. .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2013, 137 :136-149

[2] Regression of Castrate-Recurrent Prostate Cancer by a Small-Molecule Inhibitor of the Amino-Terminus Domain of the Androgen Receptor [J].

Andersen, Raymond J. ;

Mawji, Nasrin R. ;

Wang, Jun ;

Wang, Gang ;

Haile, Simon ;

Myung, Jae-Kyung ;

Watt, Kate ;

Tam, Teresa ;

Yang, Yu Chi ;

Banuelos, Carmen A. ;

Williams, David E. ;

McEwan, Iain J. ;

Wang, Yuzhou ;

Sadar, Marianne D. .

CANCER CELL, 2010, 17 (06) :535-546

[3] AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer [J].

Antonarakis, Emmanuel S. ;

Lu, Changxue ;

Wang, Hao ;

Luber, Brandon ;

Nakazawa, Mary ;

Roeser, Jeffrey C. ;

Chen, Yan ;

Mohammad, Tabrez A. ;

Chen, Yidong ;

Fedor, Helen L. ;

Lotan, Tamara L. ;

Zheng, Qizhi ;

De Marzo, Angelo M. ;

Isaacs, John T. ;

Isaacs, William B. ;

Nadal, Rosa ;

Paller, Channing J. ;

Denmeade, Samuel R. ;

Carducci, Michael A. ;

Eisenberger, Mario A. ;

Luo, Jun .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (11) :1028-1038

[4] Glucocorticoid Receptor Confers Resistance to Antiandrogens by Bypassing Androgen Receptor Blockade [J].

Arora, Vivek K. ;

Schenkein, Emily ;

Murali, Rajmohan ;

Subudhi, Sumit K. ;

Wongvipat, John ;

Balbas, Minna D. ;

Shah, Neel ;

Cai, Ling ;

Efstathiou, Eleni ;

Logothetis, Chris ;

Zheng, Deyou ;

Sawyers, Charles L. .

CELL, 2013, 155 (06) :1309-1322

[5] Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer [J].

Attard, G ;

Belldegrun, AS ;

de Bono, JS .

BJU INTERNATIONAL, 2005, 96 (09) :1241-1246

[6] Clinical and Biochemical Consequences of CYP17A1 Inhibition with Abiraterone Given with and without Exogenous Glucocorticoids in Castrate Men with Advanced Prostate Cancer [J].

Attard, Gerhardt ;

Reid, Alison H. M. ;

Auchus, Richard J. ;

Hughes, Beverly A. ;

Cassidy, Amy Mulick ;

Thompson, Emilda ;

Oommen, Nikhil Babu ;

Folkerd, Elizabeth ;

Dowsett, Mitch ;

Arlt, Wiebke ;

de Bono, Johann S. .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (02) :507-516

[7] Selective Inhibition of CYP17 With Abiraterone Acetate Is Highly Active in the Treatment of Castration-Resistant Prostate Cancer [J].

Attard, Gerhardt ;

Reid, Alison H. M. ;

A'Hern, Roger ;

Parker, Christopher ;

Oommen, Nikhil Babu ;

Folkerd, Elizabeth ;

Messiou, Christina ;

Molife, L. Rhoda ;

Maier, Gal ;

Thompson, Emilda ;

Olmos, David ;

Sinha, Rajesh ;

Lee, Gloria ;

Dowsett, Mitch ;

Kaye, Stan B. ;

Dearnaley, David ;

Kheoh, Thian ;

Molina, Arturo ;

de Bono, Johann S. .

JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (23) :3742-3748

[8] Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer [J].

Azad, Arun A. ;

Volik, Stanislav V. ;

Wyatt, Alexander W. ;

Haegert, Anne ;

Le Bihan, Stephane ;

Bell, Robert H. ;

Anderson, Shawn A. ;

McConeghy, Brian ;

Shukin, Robert ;

Bazov, Jenny ;

Youngren, Jack ;

Paris, Pamela ;

Thomas, George ;

Small, Eric J. ;

Wang, Yuzhuo ;

Gleave, Martin E. ;

Collins, Colin C. ;

Chi, Kim N. .

CLINICAL CANCER RESEARCH, 2015, 21 (10) :2315-2324

[9] Clinical Activity and Tolerability of Enzalutamide ( MDV3100) in Patients With Metastatic, Castration- Resistant Prostate Cancer Who Progress After Docetaxel and Abiraterone Treatment [J].

Badrising, Sushil ;

van der Noort, Vincent ;

van Oort, Inge M. ;

van den Berg, H. Pieter ;

Los, Maartje ;

Hamberg, Paul ;

Coenen, Jules L. ;

van den Eertwegh, Alfons J. M. ;

de Jong, Igle J. ;

Kerver, Emile D. ;

van Tinteren, Harm ;

Bergman, Andries M. .

CANCER, 2014, 120 (07) :968-975

[10] Overcoming mutation-based resistance to antiandrogens with rational drug design [J].

Balbas, Minna D. ;

Evans, Michael J. ;

Hosfield, David J. ;

Wongvipat, John ;

Arora, Vivek K. ;

Watson, Philip A. ;

Chen, Yu ;

Greene, Geoffrey L. ;

Shen, Yang ;

Sawyers, Charles L. .

ELIFE, 2013, 2

← 1 2 3 4 5 6 7 8 9 10 →