Clinical validation of circulating GDF15/MIC-1 as a marker of response to docetaxel and survival in men with metastatic castration-resistant prostate cancer.
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Embargo End Date
ICR Authors
Authors
Mahon, KL
Sutherland, SI
Lin, HM
Stockler, MR
Gurney, H
Mallesara, G
Briscoe, K
Marx, G
Higano, CS
de Bono, JS
Chi, KN
Clark, G
Breit, SN
Brown, DA
Horvath, LG
Sutherland, SI
Lin, HM
Stockler, MR
Gurney, H
Mallesara, G
Briscoe, K
Marx, G
Higano, CS
de Bono, JS
Chi, KN
Clark, G
Breit, SN
Brown, DA
Horvath, LG
Document Type
Journal Article
Date
2024-06-01
Date Accepted
2024-03-07
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.
Citation
Prostate, 2024, 84 (8), pp. 747 - 755
Source Title
Prostate
Publisher
WILEY
ISSN
0270-4137
eISSN
1097-0045
1097-0045
1097-0045
Collections
Research Team
PrCa Targeted Therapy