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January 22, 2026Cancer Research

Abstract PR024: Circulating tumor DNA methylation captures epigenetic changes in patients induced by the PRC2 inhibitor ORIC-944

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Authors

AWAmber W. WangMPMichal PawlakEAEric Ariazi

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Overview

Clinical evaluation demonstrates ORIC-944's impact on epigenetic changes in prostate cancer, suggesting enhanced treatment efficacy.

Key Points

  • This research aims to explore the epigenetic mechanisms by which ORIC-944 influences prostate cancer treatment response.
  • Evaluated clinical samples from mCRPC patients in the ORIC-944-01 Phase 1b trial.
  • Utilized DNA methylation profiling from liquid biopsies for non-invasive epigenetic analysis.
  • Developed a custom panel based on CpG-rich regions from previous DNA methylation data.
  • Enhanced AR signaling observed in tumor methylation patterns after one treatment cycle of ORIC-944.
  • No increase in neuroendocrine-associated methylation signals in any patients post-treatment.
  • Findings align with preclinical data, supporting the potential of ORIC-944 in overcoming treatment resistance.

Cite This Study

Wang et al. (2026) studied this question.

synapsesocial.com/papers/6971bfdff17b5dc6da021f50https://doi.org/10.1158/1538-7445.prostateca26-pr024
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract 6586: ORIC-944, a potent and selective allosteric PRC2 inhibitor with best-in-class properties, demonstrates combination synergy with AR pathway inhibitors in prostate cancer models2024 · 6 citations
  2. 2Abstract ND04: Discovery of ORIC-944, a novel inhibitor of PRC2 with best-in-class properties for the treatment of prostate cancer2024 · 2 citations
  3. 3Abstract 7132: Rinzimetostat blockade of PRC2 activity, a key mechanism of treatment resistance, improves response of androgen receptor pathway inhibition across a spectrum of prostate cancer models2026
  4. 4Abstract A038: Mechanisms of resistance to PD-L1/PARP1-targeted therapy in metastatic castration-resistant prostate cancer inferred by liquid biopsy2026 · 1 citations
  5. 5Epigenomic alterations associated with androgen receptor pathway inhibitor response in metastatic castration-resistant prostate cancer.2026