dc.contributor.author | Mahon, KL | |
dc.contributor.author | Sutherland, SI | |
dc.contributor.author | Lin, HM | |
dc.contributor.author | Stockler, MR | |
dc.contributor.author | Gurney, H | |
dc.contributor.author | Mallesara, G | |
dc.contributor.author | Briscoe, K | |
dc.contributor.author | Marx, G | |
dc.contributor.author | Higano, CS | |
dc.contributor.author | de Bono, JS | |
dc.contributor.author | Chi, KN | |
dc.contributor.author | Clark, G | |
dc.contributor.author | Breit, SN | |
dc.contributor.author | Brown, DA | |
dc.contributor.author | Horvath, LG | |
dc.date.accessioned | 2024-06-25T11:24:03Z | |
dc.date.available | 2024-06-25T11:24:03Z | |
dc.date.issued | 2024-06-01 | |
dc.identifier.citation | Prostate, 2024, 84 (8), pp. 747 - 755 | |
dc.identifier.issn | 0270-4137 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6269 | |
dc.identifier.eissn | 1097-0045 | |
dc.identifier.eissn | 1097-0045 | |
dc.identifier.doi | 10.1002/pros.24691 | |
dc.identifier.doi | 10.1002/pros.24691 | |
dc.description.abstract | BACKGROUND: Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC. METHODS: IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (n = 430). IL4, IL6, and GDF15 levels were measured by ELISA. Monocytes and dendritic cells were treated with 10% plasma from men with high or low GDF15 or recombinant GDF15. RESULTS: IntVal: Higher GDF15 levels at BL and Day 21 were associated with shorter overall survival (OS) (BL; p = 0.03 and Day 21; p = 0.004). IL4 and IL6 were not associated with outcomes. ExtVal: Higher GDF15 levels at BL and Day 42 predicted shorter OS (BL; p < 0.0001 and Day 42; p < 0.0001). Plasma from men with high GDF15 caused an increase in CD86 expression on monocytes (p = 0.03), but was not replicated by recombinant GDF15. CONCLUSIONS: Elevated circulating GDF15 is associated with poor prognosis in men with mCRPC receiving docetaxel and may be a marker of changes in the innate immune system in response to docetaxel resistance. These findings provide a strong rationale to consider GDF15 as a biomarker to guide a therapeutic trial of drugs targeting the innate immune system in combination with docetaxel in mCRPC. | |
dc.format.extent | 747 - 755 | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.relation.ispartof | Prostate | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Endocrinology & Metabolism | |
dc.subject | Urology & Nephrology | |
dc.subject | biomarker | |
dc.subject | docetaxel | |
dc.subject | growth differentiation factor 15 | |
dc.subject | metastatic castration-resistant prostate cancer | |
dc.subject | prognosis | |
dc.subject | therapeutic response | |
dc.subject | MACROPHAGE INHIBITORY CYTOKINE-1 | |
dc.subject | PHASE-III TRIAL | |
dc.subject | PLUS PREDNISONE | |
dc.subject | DOUBLE-BLIND | |
dc.subject | OPEN-LABEL | |
dc.subject | PLACEBO | |
dc.subject | GROWTH | |
dc.subject | CHEMOTHERAPY | |
dc.subject | MITOXANTRONE | |
dc.subject | MULTICENTER | |
dc.title | Clinical validation of circulating GDF15/MIC-1 as a marker of response to docetaxel and survival in men with metastatic castration-resistant prostate cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-03-07 | |
dc.date.updated | 2024-06-25T11:22:54Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1002/pros.24691 | |
rioxxterms.licenseref.startdate | 2024-06-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.issue | 8 | |
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/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1002/pros.24691 | |
pubs.volume | 84 | |
icr.researchteam | PrCa Targeted Therapy | |
dc.contributor.icrauthor | De Bono, Johann | |
icr.provenance | Deposited by Mr Arek Surman on 2024-06-25. Deposit type is initial. No. of files: 1. Files: The Prostate - 2024 - Mahon - Clinical validation of circulating GDF15 MIC‐1 as a marker of response to docetaxel and.pdf | |