Ceramides (lipid molecules within cells that influence many physiological functions, including cell differentiation, migration, and death) and their metabolites are thought to be involved in the development of cancer and other conditions. A new study shows that different ceramide metabolism in blacks and whites with metastatic castration-resistant prostate cancer may help explain why they tend to experience different responses to anti-prostate cancer androgen receptor pathway blockers. The findings are published on Wiley Online. cancera peer-reviewed journal of the American Cancer Society.
In two previous clinical studies, researchers observed differences in the response of blacks and whites treated with androgen receptor pathway inhibitors (which reduce or block the effects of hormones such as testosterone) for metastatic castration-resistant prostate cancer. This cancer is an aggressive type of prostate cancer that continues to grow and spread even when testosterone is suppressed to castration levels.
In one of these studies, where certain genetic ancestry-related variants in ceramide metabolism genes are associated with indicators of faster cancer progression, researchers analyzed ceramide metabolism in black and white participants in two studies before and during androgen receptor pathway inhibitor treatment.
The research team focused on the so-called carbon acyl chain length of ceramides, as there is evidence that ceramides with a carbon acyl chain length of 24 promote cell survival, while ceramides with a carbon acyl chain length of 16 induce cell death. The ratio of ceramides with carbon acyl chain lengths of 24 to 16 can influence cancer cells, with high ratios protecting cells and low ratios promoting cell death.
When researchers analyzed the blood of trial participants, they found that black patients had lower pre-treatment total ceramide levels than white patients. Among pre-treatment ceramides, black patients had higher values of the C24 to C16 ceramide ratio compared to white patients. The opposite trend was observed during treatment, with a decreased C24-to-C16-ceramide ratio in black patients, whereas a higher C24-to-C16-ceramide ratio was observed in white patients. Certain C16-, C20-, and C24-ceramides also differed between black and white patients treated in the study and were associated with shorter time to cancer progression or worse survival.
Our two previous clinical studies were unique in that they included equal numbers of black and white patients and collected blood from study participants. This has created an unprecedented opportunity to explore potential biomarkers that may be associated with patients’ self-reported race, genetic ancestry, and treatment outcome. The results of this study provide valuable observations on the potential relationship between ceramide metabolism, including genetic ancestry-related ceramide metabolism, and prostate cancer outcomes. Continued investigation of ceramide metabolism in relation to genetic ancestry has the potential to improve prostate cancer outcomes for all patients and reduce prostate cancer disparities. ”
Dr. Jennifer A. Friedman, Duke University School of Medicine Senior Author
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Reference magazines:
Piwalski, S.A.; others. (2026). Ceramide metabolism and response to androgen receptor pathway inhibition consistent with genetic ancestry in metastatic castration-resistant prostate cancer cancer. https://doi.org/10.1002/cncr.70371. https://acsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/cncr.70371
