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Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells
Published on: October 20, 2015
Cell-Free DNA Modification Dynamics in Abiraterone Acetate-Treated Prostate Cancer Patients
Juozas Gordevičius1, Algimantas Kriščiūnas1, Daniel E Groot2
1Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
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.
Insights
New biomarkers in cell-free DNA predict response to abiraterone acetate (AA) treatment in metastatic castration-resistant prostate cancer. Monitoring DNA modification variance offers insights into treatment resistance mechanisms.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) treatment relies on abiraterone acetate (AA).
- Primary resistance to AA occurs in 20-40% of patients, necessitating predictive biomarkers.
- Understanding resistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- Identify predictive biomarkers for abiraterone acetate (AA) treatment response in mCRPC.
- Investigate the mechanisms underlying AA treatment resistance.
- Explore the prognostic value of cell-free DNA (cfDNA) modification patterns.
Main Methods:
- Analyzed cfDNA methylation profiles using the Infinium Human Methylation 450K BeadChip.
- Collected and processed 108 plasma samples from 33 patients with mCRPC treated with AA.
- Compared cfDNA modification patterns between AA-sensitive and AA-resistant patient groups.
Main Results:
- Identified 30 cytosines with significant differential modification between AA-sensitive and AA-resistant patients (FDR Q < 0.05).
- Found that 21 of these cytosines were differentially modified even before treatment initiation.
- Observed a loss and subsequent return of cfDNA modification interindividual variation in AA-sensitive patients during treatment, unlike in resistant patients.
Conclusions:
- Discovered potential cfDNA methylation biomarkers for predicting AA treatment response in prostate cancer.
- Highlighted the prognostic significance of cytosine modification variance in cfDNA.
- Gained insights into prostate cancer relapse mechanisms in patients initially sensitive to AA.
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