Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications

被引：180

作者：

Aurilio, Gaetano ^{[1
]}

Cimadamore, Alessia ^{[2
]}

Mazzucchelli, Roberta ^{[2
]}

Lopez-Beltran, Antonio ^{[3
]}

Verri, Elena ^{[1
]}

Scarpelli, Marina ^{[2
]}

Massari, Francesco ^{[4
]}

Cheng, Liang ^{[5
]}

Santoni, Matteo ^{[6
]}

Montironi, Rodolfo ^{[2
]}

机构：

[1] European Inst Oncol IRCCS, Med Oncol Div Urogenital & Head & Neck Tumours, IEO, I-20141 Milan, Italy

[2] Polytech Univ Marche Reg, United Hosp, Sch Med, Sect Pathol Anat, I-60126 Ancona, Italy

[3] Cordoba Univ, Dept Surg, Med Sch, Cordoba 14071, Spain

[4] St Orsola Marcello Malpighi Hosp, Div Oncol, I-40138 Bologna, Italy

[5] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA

[6] Macerata Hosp, Oncol Unit, I-62100 Macerata, Italy

来源：

CELLS | 2020年 / 9卷 / 12期

关键词：

prostate cancer; androgen receptor; AR-V7; AR variants; AR antagonists; AR resistance; SPLICE VARIANTS; BINDING DOMAIN; MALIGNANT-TRANSFORMATION; PLASMA DNA; MUTATIONS; HORMONE; ENZALUTAMIDE; RESISTANCE; AR-V7; ABIRATERONE;

D O I：

10.3390/cells9122653

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Around 80-90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient's response to androgen ablation therapy is variable, and 20-30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs.

引用

页码：1 / 14

页数：14

共 89 条

[1] The Molecular Taxonomy of Primary Prostate Cancer [J].

Abeshouse, Adam ;

Ahn, Jaeil ;

Akbani, Rehan ;

Ally, Adrian ;

Amin, Samirkumar ;

Andry, Christopher D. ;

Annala, Matti ;

Aprikian, Armen ;

Armenia, Joshua ;

Arora, Arshi ;

Auman, J. Todd ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barbieri, Christopher E. ;

Bauer, Thomas ;

Benz, Christopher C. ;

Bergeron, Alain ;

Beroukhim, Rameen ;

Berrios, Mario ;

Bivol, Adrian ;

Bodenheimer, Tom ;

Boice, Lori ;

Bootwalla, Moiz S. ;

dos Reis, Rodolfo Borges ;

Boutros, Paul C. ;

Bowen, Jay ;

Bowlby, Reanne ;

Boyd, Jeffrey ;

Bradley, Robert K. ;

Breggia, Anne ;

Brimo, Fadi ;

Bristow, Christopher A. ;

Brooks, Denise ;

Broom, Bradley M. ;

Bryce, Alan H. ;

Bubley, Glenn ;

Burks, Eric ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Canes, David ;

Carlotti, Carlos G. ;

Carlsen, Rebecca ;

Carmel, Michel ;

Carroll, Peter R. ;

Carter, Scott L. ;

Cartun, Richard ;

Carver, Brett S. ;

Chan, June M. ;

Chang, Matthew T. ;

Chen, Yu .

CELL, 2015, 163 (04) :1011-1025

[2] Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study [J].

Aggarwal, Rahul ;

Huang, Jiaoti ;

Alumkal, Joshi J. ;

Zhang, Li ;

Feng, Felix Y. ;

Thomas, George V. ;

Weinstein, Alana S. ;

Friedl, Verena ;

Zhang, Can ;

Witte, Owen N. ;

Lloyd, Paul ;

Gleave, Martin ;

Evans, Christopher P. ;

Youngren, Jack ;

Beer, Tomasz M. ;

Rettig, Matthew ;

Wong, Christopher K. ;

True, Lawrence ;

Foye, Adam ;

Playdle, Denise ;

Ryan, Charles J. ;

Lara, Primo ;

Chi, Kim N. ;

Uzunangelov, Vlado ;

Sokolov, Artem ;

Newton, Yulia ;

Beltran, Himisha ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Stuart, Joshua M. ;

Small, Eric J. .

JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (24) :2492-+

[3] HSD3B1(1245A>C) variant regulates dueling abiraterone metabolite effects in prostate cancer [J].

Alyamani, Mohammad ;

Emamekhoo, Hamid ;

Park, Sunho ;

Taylor, Jennifer ;

Almassi, Nima ;

Upadhyay, Sunil ;

Tyler, Allison ;

Berk, Michael P. ;

Hu, Bo ;

Hwang, Tae Hyun ;

Figg, William Douglas ;

Peer, Cody J. ;

Chien, Caly ;

Koshkin, Vadim S. ;

Mendiratta, Prateek ;

Grivas, Petros ;

Rini, Brian ;

Garcia, Jorge ;

Auchus, Richard J. ;

Sharifi, Nima .

JOURNAL OF CLINICAL INVESTIGATION, 2018, 128 (08) :3333-3340

[4] 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

[5] Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer [J].

Annala, Matti ;

Vandekerkhove, Gillian ;

Khalaf, Daniel ;

Taavitsainen, Sinja ;

Beja, Kevin ;

Warner, Evan W. ;

Sunderland, Katherine ;

Kollmannsberger, Christian ;

Eigl, Bernhard J. ;

Finch, Daygen ;

Oja, Conrad D. ;

Vergidis, Joanna ;

Zulfiqar, Muhammad ;

Azad, Arun A. ;

Nykter, Matti ;

Gleave, Martin E. ;

Wyatt, Alexander W. ;

Chi, Kim N. .

CANCER DISCOVERY, 2018, 8 (04) :444-457

[6] 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

[7] ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer [J].

Armstrong, Andrew J. ;

Szmulewitz, Russell Z. ;

Petrylak, Daniel P. ;

Holzbeierlein, Jeffrey ;

Villers, Arnauld ;

Azad, Arun ;

Alcaraz, Antonio ;

Alekseev, Boris ;

Iguchi, Taro ;

Shore, Neal D. ;

Rosbrook, Brad ;

Sugg, Jennifer ;

Baron, Benoit ;

Chen, Lucy ;

Stenzl, Arnulf .

JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (32) :2974-+

[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] 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

[10] Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer [J].

Barbieri, Christopher E. ;

Baca, Sylvan C. ;

Lawrence, Michael S. ;

Demichelis, Francesca ;

Blattner, Mirjam ;

Theurillat, Jean-Philippe ;

White, Thomas A. ;

Stojanov, Petar ;

Van Allen, Eliezer ;

Stransky, Nicolas ;

Nickerson, Elizabeth ;

Chae, Sung-Suk ;

Boysen, Gunther ;

Auclair, Daniel ;

Onofrio, Robert C. ;

Park, Kyung ;

Kitabayashi, Naoki ;

MacDonald, Theresa Y. ;

Sheikh, Karen ;

Vuong, Terry ;

Guiducci, Candace ;

Cibulskis, Kristian ;

Sivachenko, Andrey ;

Carter, Scott L. ;

Saksena, Gordon ;

Voet, Douglas ;

Hussain, Wasay M. ;

Ramos, Alex H. ;

Winckler, Wendy ;

Redman, Michelle C. ;

Ardlie, Kristin ;

Tewari, Ashutosh K. ;

Mosquera, Juan Miguel ;

Rupp, Niels ;

Wild, Peter J. ;

Moch, Holger ;

Morrissey, Colm ;

Nelson, Peter S. ;

Kantoff, Philip W. ;

Gabriel, Stacey B. ;

Golub, Todd R. ;

Meyerson, Matthew ;

Lander, Eric S. ;

Getz, Gad ;

Rubin, Mark A. ;

Garraway, Levi A. .

NATURE GENETICS, 2012, 44 (06) :685-U107

← 1 2 3 4 5 6 7 8 9 →