Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/9428
Citations
Scopus Web of Science® Altmetric
?
?
Full metadata record
DC FieldValueLanguage
dc.contributor.authorScher, H.en
dc.contributor.authorBuchanan, G.en
dc.contributor.authorGerald, W.en
dc.contributor.authorButler, L.en
dc.contributor.authorTilley, W.en
dc.date.issued2004en
dc.identifier.citationEndocrine-Related Cancer, 2004; 11(3):459-476en
dc.identifier.issn1351-0088en
dc.identifier.issn1479-6821en
dc.identifier.urihttp://hdl.handle.net/2440/9428-
dc.description© 2004 by the Society for Endocrinology.en
dc.description.abstractThe categorization of prostate cancers that are progressing after castration as 'hormone-refractory' evolved from the clinical observation that surgical or medical castration (i.e. androgen ablation therapy; AAT) is not curative and, despite an initial response, virtually all tumors eventually regrow. Successful AAT is contingent on the dependence of prostate cancer cells for androgen signaling through an intracellular mediator, the androgen receptor (AR) for survival. Current preclinical and clinical data imply that the AR is expressed and continues to mediate androgen signaling after failure of AAT. As AAT does not completely eliminate circulating androgens, sufficient concentrations of dihydrotestosterone may accumulate in tumor cells to maintain AR signaling, especially in the context of upregulated receptor levels or increased sensitivity of the AR for activation. In addition, ligands of non-testicular origin or ligand-independent activation can contribute to continued AR signaling. In many cases, therefore, from the perspective of the AR, a 'hormone-refractory' classification after failure of AAT is inappropriate. Classifying prostate tumors that progress after AAT as 'castration-resistant' may be more relevant. Clinical responses to second- and third-line hormonal therapies suggest that the mechanisms of AR activation are in part a function of previously administered AAT. Accordingly, the increasing trend to utilize AAT earlier in the course of the clinical disease may have a greater influence on the genotype and phenotype of the resistant tumor. In this article, we detail strategies to inhibit the growth of prostate cancer cells that specifically target the AR in addition to those practiced traditionally that indirectly target the receptor by reducing the amount of circulating ligand. We propose that treatment regimes combining AAT with direct AR targeting strategies may provide a more complete blockade of androgen signaling, thereby preventing or significantly delaying the emergence of treatment-resistant disease.en
dc.description.statementofresponsibilityHoward I Scher, Grant Buchanan, William Gerald, Lisa M Butler and Wayne D Tilleyen
dc.language.isoenen
dc.publisherSoc Endocrinologyen
dc.subjectAnimals; Humans; Prostatic Neoplasms; Neoplasms, Hormone-Dependent; Disease Progression; Receptors, Androgen; Castration; Male; Androgen Receptor Antagonistsen
dc.titleTargeting the androgen receptor: improving outcomes for castration-resistant prostate canceren
dc.typeJournal articleen
dc.identifier.rmid0020041810en
dc.identifier.doi10.1677/erc.1.00525en
dc.identifier.pubid56024-
pubs.library.collectionMedicine publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidButler, L. [0000-0003-2698-3220]en
dc.identifier.orcidTilley, W. [0000-0003-1893-2626]en
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.