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

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.

• Authors: Juozas Gordevičius, Algimantas Kriščiūnas, Daniel E Groot, Steven M Yip, Miki Susic, Andrew Kwan, Rafal Kustra, Anthony M Joshua, Kim N Chi, Art Petronis, Gabriel Oh
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 24 Issue 14 Pg. 3317-3324 (07 15 2018) ISSN: 1557-3265 [Electronic] United States
• PMID: 29615462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2018 American Association for Cancer Research.

Chemical References

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

Topics

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