Newswire (Published: Thursday, April 23, 2020, Received: Thursday, April 23, 2020, 6:50:08 PM CDT)
Word Count: 432
2020 APR 23 (NewsRx) -- By a
“Background: Identifying treatment resistance in metastatic castration resistant prostate cancer (mCRPC) prior to initiating therapy would be a major asset in the clinical management of this highly aggressive and lethal form of the disease.
“As biopsy of metastatic lesions in this disease state is often not feasible, circulating cell free DNA (cfDNA) is an emerging tool to detect molecular drivers of resistance. While several studies have implicated the potential of mutation detection in cfDNA, DNA methylation changes have also shown promise as diagnostic and prognostic biomarkers in all stages of prostate cancer. Indeed, these tumor-derived DNA methylation patterns are detectable in circulation.
“However, the dynamics of the methylome in cfDNA has not been extensively studied, especially during treatment with current androgen-targeting agents. Results: In this study, we performed genome-wide methylation sequencing analysis of cfDNA derived from mCRPC patients undergoing treatment with either Abiraterone acetate or Enzalutamide. Analysis of sequentially collected plasma cfDNA samples was performed, examining changes in the cfDNA methylome from prior to starting treatment (baseline), 12-weeks during treatment and upon clinical progression. We developed a comprehensive analysis pipeline to identify differentially methylated regions within each patient during treatment. We examined the frequency of genome wide cfDNA methylation changes across all patients and correlated these patterns with time to clinical progression. Overall, changes in well-established prostate cancer methylation markers and alterations in key pathways, such as Wnt and neuronal development, were detectable in cfDNA. Patients that maintained methylation changes from baseline to week-12 and until progression tended to have a longer time to clinical progression (TTP). Importantly, we observed that markers associated with a highly aggressive form of the disease, Neuroendocrine-CRPC (NE-CRPC), could be detected prior to initiating treatment and were associated with a faster TTP.
“Conclusions: Treatment-related methylation changes associated with TTP highlights the potential of monitoring cfDNA methylome during therapy in mCRPC. Our findings also suggest that detection of NE-CRPC associated methylation signatures in earlier stages of treatment may serve as predictive markers of response to androgen-targeting agents.”
This preprint may not have been peer-reviewed. For more information on this research see: http://biorxiv.org/content/10.1101/2020.04.08.032565v1
Keywords for this news article include: Androgens, Biomarkers, Cancer, Diagnostics and Screening, Drugs and Therapies, Health and Medicine, Oncology, Oncology - Prostate Cancer, Prostate Cancer, Prostatic Neoplasms.
(Our reports deliver fact-based news of research and discoveries from around the world.)