Cell-free DNA modification dynamics in abiraterone acetate-treated prostate cancer patients
J Gordevičius, A Kriščiūnas, DE Groot, SM Yip… - Clinical Cancer …, 2018 - AACR
Clinical Cancer Research, 2018•AACR
Purpose: Primary resistance to abiraterone acetate (AA), a key medication for the treatment
of metastatic castration-resistant prostate cancer, occurs in 20% to 40% of patients. We aim
to identify predictive biomarkers for AA-treatment response and understand the mechanisms
related to treatment resistance. Experimental Design: We used the Infinium Human
Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA
(cfDNA) in 108 plasma samples collected from 33 AA-treated patients. Results: Thirty …
of metastatic castration-resistant prostate cancer, occurs in 20% to 40% of patients. We aim
to identify predictive biomarkers for AA-treatment response and understand the mechanisms
related to treatment resistance. Experimental Design: We used the Infinium Human
Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA
(cfDNA) in 108 plasma samples collected from 33 AA-treated patients. Results: Thirty …
Abstract
Purpose: Primary resistance to abiraterone acetate (AA), a key medication for the treatment of metastatic castration-resistant prostate cancer, occurs in 20% to 40% of patients. We aim to identify predictive biomarkers for AA-treatment response and understand the mechanisms related to treatment resistance.
Experimental Design: We used the Infinium Human Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA (cfDNA) in 108 plasma samples collected from 33 AA-treated patients.
Results: Thirty cytosines showed significant modification differences (FDR Q < 0.05) between AA-sensitive and AA-resistant patients during the treatment, of which 21 cytosines were differentially modified prior to treatment. In addition, AA-sensitive patients, but not AA-resistant patients, lost interindividual variation of cfDNA modification shortly after starting AA treatment, but such variation returned to initial levels in the later phases of treatment.
Conclusions: Our findings provide a list of potential biomarkers for predicting AA-treatment response, highlight the prognostic value of using cytosine modification variance as biomarkers, and shed new insights into the mechanisms of prostate cancer relapse in AA-sensitive patients. Clin Cancer Res; 24(14); 3317–24. ©2018 AACR.
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