Biology of progressive, castration-resistant prostate cancer: Directed therapies targeting the androgen-receptor signaling axis Journal Article
| Authors: | Scher, H. I.; Sawyers, C. L. |
| Article Title: | Biology of progressive, castration-resistant prostate cancer: Directed therapies targeting the androgen-receptor signaling axis |
| Abstract: | Prostate cancers that are progressing on medical and surgical therapies designed to ablate the action of androgens continue to express androgen receptor (AR) and to depend on signaling through the receptor for growth. A more clinically relevant classification of castration-resistant disease focuses on the mechanisms of receptor activation, which include (1) changes in the level of ligand(s) in tumor tissue; (2) increased levels of the protein due to gene amplification or altered mRNA expression; (3) activating mutations in the receptor that affect structure and function; (4) changes in coregulatory molecules including coactivators and corepressors; and (5) factors that lead to activation of the receptor independent of the level of ligand or receptor allowing kinase cross talk. From an AR perspective, the term "hormone refractory" is inappropriate. On the basis of this schema, we discuss strategies that are focused on the AR either directly or indirectly, as single agents or in combination, that are in clinical development. © 2005 by American Society of Clinical Oncology. |
| Keywords: | signal transduction; protein expression; cancer surgery; gene mutation; histone deacetylase inhibitor; clinical trial; disease course; review; cancer growth; drug withdrawal; monotherapy; nonhuman; protein function; metabolism; gene amplification; protein targeting; drug effect; gonadorelin; cancer resistance; docetaxel; prostate cancer; prostatic neoplasms; drug antagonism; messenger rna; disease progression; prostate tumor; finasteride; vorinostat; androgen receptor; diethylstilbestrol; drug blood level; aminoglutethimide; antiandrogen; bicalutamide; flutamide; hydrocortisone; ketoconazole; nilutamide; castration; orchiectomy; receptors, androgen; cancer classification; protein structure; everolimus; arylbutyric acid derivative; fulvestrant; megestrol acetate; steroid 5alpha reductase inhibitor; geldanamycin; ansamycin derivative; steroid 17alpha monooxygenase |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 23 |
| Issue: | 32 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2005-11-10 |
| Start Page: | 8253 |
| End Page: | 8261 |
| Language: | English |
| DOI: | 10.1200/jco.2005.03.4777 |
| PUBMED: | 16278481 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 326" - "Export Date: 24 October 2012" - "CODEN: JCOND" - "Source: Scopus" |
