Enzalutamide therapy for advanced prostate cancer: efficacy, resistance and beyond

被引：41

作者：

Linder, Simon ^{[1
]}

van der Poel, Henk G. ^{[2
]}

Bergman, Andries M. ^{[3
,4
]}

Zwart, Wilbert ^{[1
,5
,6
]}

Prekovic, Stefan ^{[1
]}

机构：

[1] Netherlands Canc Inst, Oncode Inst, Div Oncogen, Amsterdam, Netherlands

[2] Netherlands Canc Inst, Div Urol, Amsterdam, Netherlands

[3] Netherlands Canc Inst, Div Med Oncol, Amsterdam, Netherlands

[4] Netherlands Canc Inst, Div Oncogen, Amsterdam, Netherlands

[5] Eindhoven Univ Technol, Lab Chem Biol, Eindhoven, Netherlands

[6] Eindhoven Univ Technol, Dept Biomed Engn, Inst Complex Mol Syst, Eindhoven, Netherlands

来源：

关键词：

enzalutamide; treatment resistance; biomarkers; androgen receptor; mutations; prostate cancer; mCRPC; androgen deprivation therapy; docetaxel; ANDROGEN-DEPRIVATION THERAPY; MITOXANTRONE PLUS PREDNISONE; RECEPTOR SPLICE VARIANT; ABIRATERONE ACETATE; ANTITUMOR-ACTIVITY; CLINICAL ACTIVITY; PHASE-II; GLUCOCORTICOID-RECEPTOR; MUTATIONAL LANDSCAPE; SELECTIVE-INHIBITION;

D O I：

10.1530/ERC-18-0289

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The androgen receptor drives the growth of metastatic castration-resistant prostate cancer. This has led to the development of multiple novel drugs targeting this hormone-regulated transcription factor, such as enzalutamide - a potent androgen receptor antagonist. Despite the plethora of possible treatment options, the absolute survival benefit of each treatment separately is limited to a few months. Therefore, current research efforts are directed to determine the optimal sequence of therapies, discover novel drugs effective in metastatic castration-resistant prostate cancer and define patient subpopulations that ultimately benefit from these treatments. Molecular studies provide evidence on which pathways mediate treatment resistance and may lead to improved treatment for metastatic castration-resistant prostate cancer. This review provides, firstly a concise overview of the clinical development, use and effectiveness of enzalutamide in the treatment of advanced prostate cancer, secondly it describes translational research addressing enzalutamide response vs resistance and lastly highlights novel potential treatment strategies in the enzalutamide-resistant setting.

引用

页码：R31 / R52

页数：22

共 208 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] The Effect of Prior Androgen Synthesis Inhibition on Outcomes of Subsequent Therapy With Docetaxel in Patients With Metastatic Castrate-Resistant Prostate Cancer [J].

Aggarwal, Rahul ;

Halabi, Susan ;

Kelly, William Kevin ;

George, Daniel ;

Mahoney, John F. ;

Millard, Frederick ;

Stadler, Walter M. ;

Morris, Michael J. ;

Kantoff, Philip ;

Monk, J. Paul ;

Carducci, Michael ;

Small, Eric J. .

CANCER, 2013, 119 (20) :3636-3643

[3]

[Anonymous], 2016, Ann. Oncol, DOI [10.1093/annonc/mdw372.04, DOI 10.1093/ANNONC/MDW372.04]

[4] Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting [J].

Antonarakis, E. S. ;

Armstrong, A. J. ;

Dehm, S. M. ;

Luo, J. .

PROSTATE CANCER AND PROSTATIC DISEASES, 2016, 19 (03) :231-241

[5] Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association with Overall Survival [J].

Antonarakis, Emmanuel S. ;

Small, Eric J. ;

Petrylak, Daniel P. ;

Quinn, David I. ;

Kibel, Adam S. ;

Chang, Nancy N. ;

Dearstyne, Erica ;

Harmon, Matt ;

Campogan, Dwayne ;

Haynes, Heather ;

Tuyen Vu ;

Sheikh, Nadeem A. ;

Drake, Charles G. .

CLINICAL CANCER RESEARCH, 2018, 24 (19) :4662-4671

[6] Clinical Significance of Androgen Receptor Splice Variant-7 mRNA Detection in Circulating Tumor Cells of Men With Metastatic Castration- Resistant Prostate Cancer Treated With First- and Second-Line Abiraterone and Enzalutamide [J].

Antonarakis, Emmanuel S. ;

Lu, Changxue ;

Luber, Brandon ;

Wang, Hao ;

Chen, Yan ;

Zhu, Yezi ;

Silberstein, John L. ;

Taylor, Maritza N. ;

Maughan, Benjamin L. ;

Denmeade, Samuel R. ;

Pienta, Kenneth J. ;

Paller, Channing J. ;

Carducci, Michael A. ;

Eisenberger, Mario A. ;

Luo, Jun .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (19) :2149-+

[7] Enzalutamide: the emperor of all anti-androgens [J].

Antonarakis, Emmanuel S. .

TRANSLATIONAL ANDROLOGY AND UROLOGY, 2013, 2 (02) :119-120

[8] 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

[9] Platinum-Based Chemotherapy for Variant Castrate-Resistant Prostate Cancer [J].

Aparicio, Ana M. ;

Harzstark, Andrea L. ;

Corn, Paul G. ;

Wen, Sijin ;

Araujo, John C. ;

Tu, Shi-Ming ;

Pagliaro, Lance C. ;

Kim, Jeri ;

Millikan, Randall E. ;

Ryan, Charles ;

Tannir, Nizar M. ;

Zurita, Amado J. ;

Mathew, Paul ;

Arap, Wadih ;

Troncoso, Patricia ;

Thall, Peter F. ;

Logothetis, Christopher J. .

CLINICAL CANCER RESEARCH, 2013, 19 (13) :3621-3630

[10] 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

← 1 2 3 4 5 6 7 8 9 10 →