Cell-Free DNA Modification Dynamics in Abiraterone Acetate-Treated Prostate Cancer Patients

Clin Cancer Res. 2018 Jul 15;24(14):3317-3324. doi: 10.1158/1078-0432.CCR-18-0101. Epub 2018 Apr 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abiraterone Acetate / administration & dosage
  • Abiraterone Acetate / adverse effects
  • Abiraterone Acetate / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor*
  • Cell-Free Nucleic Acids*
  • Epigenesis, Genetic / drug effects
  • Humans
  • Male
  • Prognosis
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • Abiraterone Acetate