Cancer
Ceramide profiles may predict ARPI outcomes in metastatic prostate cancer
Clinical Takeaway: Consider emerging evidence that specific ceramide profiles—particularly C24:C16 ratios and Cer(d18:1/20:0)—may help identify patients more or less likely to benefit from ARPI, though validation is needed before clinical use.
Biomarkers tied to ceramide metabolism could help personalize androgen receptor pathway inhibitor (ARPI) therapy and shed light on outcome disparities in prostate cancer.
In two prospective cohorts (Abi Race and PANTHER), investigators analyzed fasting serum metabolomics from 109 patients with metastatic castration-resistant prostate cancer (mCRPC), including 50 Black and 59 White patients with paired pre- and on-treatment samples. Pretreatment total ceramide levels were consistently lower in Black patients, alongside higher baseline C24:C16 ceramide ratios—patterns that shifted during ARPI therapy, with lower ratios emerging in Black patients and higher ratios in White patients.
Distinct ceramide species correlated with outcomes. Among Black patients, higher baseline Cer(d18:1/20:0) was associated with significantly worse radiographic progression-free survival (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.06–15.2) and overall survival (HR, 4.82; 95% CI, 1.51–15.4). Other ceramides demonstrated race-specific associations with time to PSA progression; for example, higher Cer(d18:2/16:0) and Cer(d18:2/24:0) were linked to longer PSA control in Black patients, while different ceramide species showed benefit in White patients.
Across both trials, multiple ceramide metabolites—more than 20 species in some analyses—were associated with treatment response using machine learning–based selection. Prior clinical outcomes data from these cohorts showed 24-month radiographic PFS of 61% in Black versus 38% in White patients and 36-month overall survival of 68% versus 50%, respectively, underscoring clinically meaningful differences.
“Distinct ceramide species…have potential to serve as genetic ancestry–concordant, predictive indicators of response,” the authors noted, emphasizing the need for validation.
Overall, the findings highlight ceramide metabolism as a promising, biologically grounded pathway for biomarker development and therapeutic targeting in mCRPC.
Source: Piwarski SA, et al. (2026, June 1). Cancer. Genetic ancestry-concordant ceramide metabolism and response to androgen receptor pathway inhibition in metastatic castration-resistant prostate cancer