Integrative liquid biopsy reveals resistance mechanisms in prostate cancer, with NCI's Adam Sowalsky, PhD
Learn how 6-base sequencing can reveal a more dynamic, non-invasive view of treatment response and disease progression.
This webinar is best for:
- Translational and cancer genomics researchers, liquid biopsy and ctDNA scientists, and scientists and R&D leaders working in precision oncology
Watch Dr. Adam Sowalsky from the National Cancer Institute (NCI) explain how he used biomodal's duet multiomics solution evoC technology (6-base sequencing) to redefine what liquid biopsy can reveal. Using serial plasma samples from a phase 2 trial, his research went beyond revealing mutations or even methylation detection to uncover gene expression, unlocking an understanding of tumour phenotypes and emerging resistance patterns over time, all from low-input cfDNA samples.
Watch the recording now to see how biomodal's duet multiomics solution evoC can capture DNA sequence, epigenetics, and functional insights from cfDNA – revealing resistance mechanisms in prostate cancer that conventional genomics would have missed.
What you will learn:
- How a single assay integrates genetic, 5mC, 5hmC, and inferred gene expression to reconstruct tumour biology from cfDNA
- Insights from distinct epigenetic patterns (5mC and 5hmC) that reveal tumour states and early response signals missed by conventional epigenetic methods
- Direct inference of tumour transcriptional programs from plasma to track treatment response and emerging resistance over time
The speaker
Adam Sowalsky, Ph.D.
Senior Investigator, National Cancer Institute
Dr. Adam Sowalsky is a Senior Investigator in the Genitourinary Malignancies Branch of the National Cancer Institute (NCI), where he leads the Prostate Cancer Genetics Section. He leads the NIH Scientific Interest Group on Liquid Biopsies. The central theme of Dr. Sowalsky's research is understanding the biology of the molecular events associated with prostate cancer development, progression, and resistance to therapy. His research uses patient samples from NCI clinical trials to track how subclonal architecture drives disease progression and therapy failure. Dr. Sowalsky received his Ph.D. from Tufts University's Graduate School of Biomedical Sciences and conducted postdoctoral training at Harvard Medical School and Beth Israel Deaconess Medical Center.
Dr. Sowalsky's talk is entitled "Dual ctDNA 5mC/5hmC methylomics and clonal reconstruction reveal tumor transcription and resistance in metastatic prostate cancer".
This webinar was originally broadcast on 17 June 2026.
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Is there an abstract available for this webinar?
Abstract: Liquid biopsies can detect actionable mutations and infer broad tumor states from genome-wide cfDNA measurements, but quantitative transcriptome-like phenotyping at single gene resolution still largely requires tissue. Here, we asked whether 6-base whole-genome sequencing that jointly quantifies 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) could infer gene expression directly from plasma. We applied this framework to plasma from patients enrolled in a phase 2 clinical trial of the PARP inhibitor olaparib plus the PD-L1 inhibitor durvalumab for metastatic castration-resistant prostate cancer. Inferred plasma transcriptomes distinguished adenocarcinoma vs. neuroendocrine phenotypes and identified a noncanonical WNT5A-associated signature linked to poor clinical response. Integrating longitudinal cfDNA methylomic profiles with phylogenetic reconstruction further revealed two resistance trajectories: one featuring high tumor heterogeneity with persistent AR signaling, and another marked by an AR-independent, stem-like program with metabolic reprogramming. These findings demonstrate that ctDNA can inform phenotype-driven tumor biology at gene-level resolution, integrating epigenetic modifications, inferred transcriptional programs, and clonal dynamics as a function of treatment response.
Has this research been published?
This talk has been presented at AACR 2026, and is available as a preprint article.