dc.contributor.author | Sowalsky, AG | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Lis, RT | |
dc.contributor.author | Coleman, I | |
dc.contributor.author | Gurel, B | |
dc.contributor.author | Bogdan, D | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Russo, JW | |
dc.contributor.author | Bright, JR | |
dc.contributor.author | Whitlock, NC | |
dc.contributor.author | Trostel, SY | |
dc.contributor.author | Ku, AT | |
dc.contributor.author | Patel, RA | |
dc.contributor.author | True, LD | |
dc.contributor.author | Welti, J | |
dc.contributor.author | Jimenez-Vacas, JM | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Neeb, A | |
dc.contributor.author | Sprenger, CT | |
dc.contributor.author | Swain, A | |
dc.contributor.author | Wilkinson, S | |
dc.contributor.author | Karzai, F | |
dc.contributor.author | Dahut, WL | |
dc.contributor.author | Balk, SP | |
dc.contributor.author | Corey, E | |
dc.contributor.author | Nelson, PS | |
dc.contributor.author | Haffner, MC | |
dc.contributor.author | Plymate, SR | |
dc.contributor.author | de Bono, JS | |
dc.contributor.author | Sharp, A | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-08-31T14:44:26Z | |
dc.date.available | 2022-08-31T14:44:26Z | |
dc.date.issued | 2022-08-15 | |
dc.identifier | 707390 | |
dc.identifier.citation | Clinical Cancer Research, 2022, 28 (16), pp. 3509 - 3525 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5360 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-22-0851 | |
dc.description.abstract | PURPOSE: Therapies targeting the androgen receptor (AR) have improved the outcome for patients with castration-sensitive prostate cancer (CSPC). Expression of the constitutively active AR splice variant-7 (AR-V7) has shown clinical utility as a predictive biomarker of AR-targeted therapy resistance in castration-resistant prostate cancer (CRPC), but its importance in CSPC remains understudied. EXPERIMENTAL DESIGN: We assessed different approaches to quantify AR-V7 mRNA and protein in prostate cancer cell lines, patient-derived xenograft (PDX) models, publicly available cohorts, and independent institutional clinical cohorts, to identify reliable approaches for detecting AR-V7 mRNA and protein and its association with clinical outcome. RESULTS: In CSPC and CRPC cohorts, AR-V7 mRNA was much less abundant when detected using reads across splice boundaries than when considering isoform-specific exonic reads. The RM7 AR-V7 antibody had increased sensitivity and specificity for AR-V7 protein detection by immunohistochemistry (IHC) in CRPC cohorts but rarely identified AR-V7 protein reactivity in CSPC cohorts, when compared with the EPR15656 AR-V7 antibody. Using multiple CRPC PDX models, we demonstrated that AR-V7 expression was exquisitely sensitive to hormonal manipulation. In CSPC institutional cohorts, AR-V7 protein quantification by either assay was associated neither with time to development of castration resistance nor with overall survival, and intense neoadjuvant androgen-deprivation therapy did not lead to significant AR-V7 mRNA or staining following treatment. Neither pre- nor posttreatment AR-V7 levels were associated with volumes of residual disease after therapy. CONCLUSIONS: This study demonstrates that further analytical validation and clinical qualification are required before AR-V7 can be considered for clinical use in CSPC as a predictive biomarker. | |
dc.format | Print | |
dc.format.extent | 3509 - 3525 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Clinical Cancer Research | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Androgen Antagonists | |
dc.subject | Biomarkers | |
dc.subject | Castration | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.subject | Protein Isoforms | |
dc.subject | RNA, Messenger | |
dc.subject | Receptors, Androgen | |
dc.title | Assessment of Androgen Receptor Splice Variant-7 as a Biomarker of Clinical Response in Castration-Sensitive Prostate Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-06-08 | |
dc.date.updated | 2022-08-31T14:43:15Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-22-0851 | |
rioxxterms.licenseref.startdate | 2022-08-15 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35695870 | |
pubs.issue | 16 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1158/1078-0432.ccr-22-0851 | |
pubs.volume | 28 | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | PrCa Targeted Therapy | |
dc.contributor.icrauthor | Gurel, Bora | |
dc.contributor.icrauthor | Bogdan, Denisa Ioana | |
dc.contributor.icrauthor | Swain, Amanda | |
dc.contributor.icrauthor | De Bono, Johann | |
dc.contributor.icrauthor | Sharp, Adam | |
icr.provenance | Deposited by Mr Arek Surman on 2022-08-31. Deposit type is initial. No. of files: 1. Files: 3509.pdf | |