Targeting molecular resistance in castration-resistant prostate cancer

被引:47
作者
Chandrasekar, Thenappan [1 ]
Yang, Joy C. [1 ]
Gao, Allen C. [1 ]
Evans, Christopher P. [1 ]
机构
[1] Univ Calif Davis, Dept Urol, Davis, CA 95616 USA
来源
BMC MEDICINE | 2015年 / 13卷
关键词
Castration-resistant; Disease progression; Drug resistance; Prostatic neoplasms; ANDROGEN RECEPTOR GENE; OVERCOMES ENZALUTAMIDE RESISTANCE; III BETA-TUBULIN; SPLICE VARIANT; ABIRATERONE ACETATE; CYP17A1; INHIBITION; INCREASED SURVIVAL; CLINICAL ACTIVITY; PLUS PREDNISONE; CELL BIOLOGY;
D O I
10.1186/s12916-015-0457-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Multiple mechanisms of resistance contribute to the inevitable progression of hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC). Currently approved therapies for CRPC include systemic chemotherapy (docetaxel and cabazitaxel) and agents targeting the resistance pathways leading to CRPC, including enzalutamide and abiraterone. While there is significant survival benefit, primary and secondary resistance to these therapies develops rapidly. Up to one-third of patients have primary resistance to enzalutamide and abiraterone; the remaining patients eventually progress on treatment. Understanding the mechanisms of resistance resulting in progression as well as identifying new targetable pathways remains the focus of current prostate cancer research. We review current knowledge of mechanisms of resistance to the currently approved treatments, development of adjunctive therapies, and identification of new pathways being targeted for therapeutic purposes.
引用
收藏
页数:10
相关论文
共 115 条
  • [1] Agoulnik IU, 2008, ADV EXP MED BIOL, V617, P245, DOI 10.1007/978-0-387-69080-3_23
  • [2] Cabazitaxel Remains Active in Patients Progressing After Docetaxel Followed by Novel Androgen Receptor Pathway Targeted Therapies
    Al Nakouzi, Nader
    Le Moulec, Sylvestre
    Albiges, Laurence
    Wang, Chris
    Beuzeboc, Philippe
    Gross-Goupil, Marine
    Rouge, Thibault de la Motte
    Guillot, Aline
    Gajda, Dorota
    Massard, Christophe
    Gleave, Martin
    Fizazi, Karim
    Loriot, Yohann
    [J]. EUROPEAN UROLOGY, 2015, 68 (02) : 228 - 235
  • [3] Regression of Castrate-Recurrent Prostate Cancer by a Small-Molecule Inhibitor of the Amino-Terminus Domain of the Androgen Receptor
    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.
    [J]. CANCER CELL, 2010, 17 (06) : 535 - 546
  • [4] [Anonymous], J CLIN ONCOL
  • [5] [Anonymous], J CLIN ONCOL
  • [6] AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer
    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
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (11) : 1028 - 1038
  • [7] Clinical and Biochemical Consequences of CYP17A1 Inhibition with Abiraterone Given with and without Exogenous Glucocorticoids in Castrate Men with Advanced Prostate Cancer
    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.
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (02) : 507 - 516
  • [8] Selective Inhibition of CYP17 With Abiraterone Acetate Is Highly Active in the Treatment of Castration-Resistant Prostate Cancer
    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.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (23) : 3742 - 3748
  • [9] Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer
    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.
    [J]. CLINICAL CANCER RESEARCH, 2015, 21 (10) : 2315 - 2324
  • [10] Novel and next-generation androgen receptor-directed therapies for prostate cancer: Beyond abiraterone and enzalutamide
    Bambury, Richard M.
    Rathkopf, Dana E.
    [J]. UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 2016, 34 (08) : 348 - 355