Targeting the androgen receptor pathway in prostate cancer Journal Article
| Authors: | Chen, Y.; Sawyers, C. L.; Scher, H. I. |
| Article Title: | Targeting the androgen receptor pathway in prostate cancer |
| Abstract: | When prostate cancers progress following androgen depletion therapy, there are currently few treatment options with only one, docetaxel, that has been shown to prolong life. Recent work has shown that castration-resistant prostate cancers (CRPCs) continue to depend on androgen receptor (AR) signaling which is reactivated despite low serum androgen levels. Currently available AR-targeted therapy, including GnRH agonists and antiandrogens, cannot completely shut down AR signaling. Several mechanisms that enhance AR signaling in an androgen-depleted environment have been elucidated. These include AR mutations that allow activation by low androgen levels or by other endogenous steroids, AR overexpression, increased local intracrine synthesis of androgens, and upregulation of tyrosine kinase pathways. This has led to the development of a number of novel agents targeting the AR signaling pathway, including more effective antiandrogens, inhibitors of CYP17, an enzyme required for androgen synthesis, inhibitors of 5α-reductase, inhibitors of HSP90 which protects AR from degradation, inhibitors of histone deacetylases which is required for optimal AR-mediated transcription, as well as inhibitors of tyrosine kinase inhibitors. Many of these strategies are currently being tested in clinical trials in CRPC. © 2008 Elsevier Ltd. All rights reserved. |
| Keywords: | signal transduction; cancer survival; unclassified drug; gene mutation; overall survival; androgen; histone deacetylase inhibitor; clinical trial; review; erlotinib; cancer growth; drug efficacy; nonhuman; antineoplastic agents; adjuvant therapy; pancreas resection; antineoplastic agent; protein function; prostate specific antigen; animals; gene overexpression; unindexed drug; enzyme inhibition; protein targeting; antineoplastic activity; enzyme activation; tumor xenograft; dasatinib; cancer resistance; docetaxel; drug receptor binding; prostate cancer; protein kinase inhibitors; prostatic neoplasms; oncogene; cancer cell; drug response; gefitinib; androgen antagonists; finasteride; vorinostat; heat shock protein 90 inhibitor; tanespimycin; hsp90 heat-shock proteins; androgen receptor; prostate hypertrophy; drug bioavailability; metastasis potential; aminoglutethimide; antiandrogen; bicalutamide; cyproterone acetate; dutasteride; flutamide; ketoconazole; mdv 3100; nilutamide; castration; orchiectomy; receptors, androgen; cancer control; trastuzumab; protein determination; panobinostat; histone deacetylases; disease exacerbation; ligand binding; lapatinib; phosphotransferase inhibitor; bms 641988; pertuzumab; hormone determination; depsipeptide; disease activity; hormone action; androgen synthesis |
| Journal Title: | Current Opinion in Pharmacology |
| Volume: | 8 |
| Issue: | 4 |
| ISSN: | 1471-4892 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2008-08-01 |
| Start Page: | 440 |
| End Page: | 448 |
| Language: | English |
| DOI: | 10.1016/j.coph.2008.07.005 |
| PUBMED: | 18674639 |
| PROVIDER: | scopus |
| PMCID: | PMC2574839 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 84" - "Export Date: 17 November 2011" - "CODEN: COPUB" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work