Clinical validation of circulating GDF15/MIC‐1 as a marker of response to docetaxel and survival in men with metastatic castration‐resistant prostate cancer
Clinical validation of circulating GDF15/MIC‐1 as a marker of response to docetaxel and survival in men with metastatic castration‐resistant prostate cancer
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. While androgen deprivation therapy is initially effective for metastatic disease, ultimately the disease progresses to the castration‐resistant state. Docetaxel was the first agent to provide a survival benefit in metastatic, castration‐resistant prostate cancer and, despite the addition of new therapeutic agents, remains central to the treatment paradigm. However, docetaxel significantly benefits only half of men, with prostate‐specific antigen response rates of 45%–60%.
The internal validation: Plasma samples at baseline and Day 21 docetaxel. The external validation: Serum samples at baseline and Day 42 of docetaxel. interleukin 4, interleukin 6, 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.
The internal validation: Higher GDF15 levels at baseline and Day 21 were associated with shorter overall survival. interleukin 4 and interleukin 6 were not associated with outcomes. The external validation: Higher GDF15 levels at baseline and Day 42 predicted shorter overall survival. Plasma from men with high GDF15 caused an increase in CD86 expression on monocytes, but was not replicated by recombinant GDF15.
Elevated circulating GDF15 is associated with poor prognosis in men with metastatic castration‐resistant prostate cancer 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 metastatic castration‐resistant prostate cancer.
https://onlinelibrary.wiley.com/doi/pdf/10.1002/pros.24691