Drug discovery in prostate cancer mouse models

被引:12
作者
Valkenburg, Kenneth C. [1 ]
Pienta, Kenneth J. [1 ,2 ,3 ,4 ]
机构
[1] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Dept Urol, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Dept Oncol, Baltimore, MD 21287 USA
[3] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Dept Pharmacol & Mol Sci, Baltimore, MD 21287 USA
[4] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Dept Chem & Biomol Engn, Baltimore, MD 21287 USA
关键词
drug discovery; model organism; mouse models; prostate cancer; TISSUE-SPECIFIC EXPRESSION; CARCINOMA-CELL-LINE; PATIENT-DERIVED XENOGRAFTS; INTRAEPITHELIAL NEOPLASIA; ANDROGEN RECEPTOR; PTEN LOSS; CONDITIONAL DELETION; BONE METASTASIS; BETA-CATENIN; MICE LACKING;
D O I
10.1517/17460441.2015.1052790
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: The mouse is an important, though imperfect, organism with which to model human disease and to discover and test novel drugs in a preclinical setting. Many experimental strategies have been used to discover new biological and molecular targets in the mouse, with the hopes of translating these discoveries into novel drugs to treat prostate cancer in humans. Modeling prostate cancer in the mouse, however, has been challenging, and often drugs that work in mice have failed in human trials. Areas covered: The authors discuss the similarities and differences between mice and men; the types of mouse models that exist to model prostate cancer; practical questions one must ask when using a mouse as a model; and potential reasons that drugs do not often translate to humans. They also discuss the current value in using mouse models for drug discovery to treat prostate cancer and what needs are still unmet in field. Expert opinion: With proper planning and following practical guidelines by the researcher, the mouse is a powerful experimental tool. The field lacks genetically engineered metastatic models, and xenograft models do not allow for the study of the immune system during the metastatic process. There remain several important limitations to discovering and testing novel drugs in mice for eventual human use, but these can often be overcome. Overall, mouse modeling is an essential part of prostate cancer research and drug discovery. Emerging technologies and better and ever-increasing forms of communication are moving the field in a hopeful direction.
引用
收藏
页码:1011 / 1024
页数:14
相关论文
共 166 条
[1]  
Abate-Shen C, 2003, CANCER RES, V63, P3886
[2]   Molecular genetics of prostate cancer [J].
Abate-Shen, C ;
Shen, MM .
GENES & DEVELOPMENT, 2000, 14 (19) :2410-2434
[3]   Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia [J].
Abdulkadir, SA ;
Magee, JA ;
Peters, TJ ;
Kaleem, Z ;
Naughton, CK ;
Humphrey, PA ;
Milbrandt, J .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (05) :1495-1503
[4]   Comparative study of PSMA expression in the prostate of mouse, dog, monkey, and human [J].
Aggarwal, Saurabh ;
Ricklis, Rebecca M. ;
Williams, Simon A. ;
Denmeade, Samuel R. .
PROSTATE, 2006, 66 (09) :903-910
[5]   The role of murine models of prostate cancer in drug target discovery and validation [J].
Ahmad, Imran ;
Sansom, Owen J. ;
Leung, Hing Y. .
EXPERT OPINION ON DRUG DISCOVERY, 2009, 4 (08) :879-888
[6]  
An ZL, 1998, PROSTATE, V34, P169
[7]   Neuroendocrine Prostate Cancer Xenografts With Large-Cell and Small-Cell Features Derived From a Single Patient's Tumor: Morphological, Immunohistochemical, and Gene Expression Profiles [J].
Aparicio, Ana ;
Tzelepi, Vasiliki ;
Araujo, John C. ;
Guo, Charles C. ;
Liang, Shoudan ;
Troncoso, Patricia ;
Logothetis, Christopher J. ;
Navone, Nora M. ;
Maity, Sankar N. .
PROSTATE, 2011, 71 (08) :846-856
[8]   Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten [J].
Backman, SA ;
Ghazarian, D ;
So, K ;
Sanchez, O ;
Wagner, KU ;
Hennighausen, L ;
Suzuki, A ;
Tsao, MS ;
Chapman, WB ;
Stambolic, V ;
Mak, TW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (06) :1725-1730
[9]   FLUCTUATIONS IN PLASMA TESTOSTERONE LEVELS IN ADULT MALE RATS AND MICE [J].
BARTKE, A ;
STEELE, RE ;
MUSTO, N ;
CALDWELL, BV .
ENDOCRINOLOGY, 1973, 92 (04) :1223-1228
[10]   EVIDENCE FOR EPISODIC SECRETION OF TESTOSTERONE IN LABORATORY MICE [J].
BARTKE, A ;
DALTERIO, S .
STEROIDS, 1975, 26 (06) :749-756